Effects of laparoscopic models on anaerobic bacterial growth with bacteroides fragilis in experimentally induced peritonitis

BACKGROUND: Previous reports of recurrent intra-abdominal abcess formation after the laparoscopic treatment of perforated acute appendicitis led us to investigate the possible effects of gas insufflation on the spread of infection. We previously showed that Escherichia coli counts were significantly higher in a laparoscopy group that underwent carbon dioxide (CO2) insufflation than in control and laparotomy groups. The aim of this study is to investigate the effects of intra-abdominal CO2 and nitrous oxide (N2O) insufflation on anaerobic bacterial growth in a rat model. METHODS: A standard strain of Bacteroides fragilis (ATCC 25285) was injected intraperitoneally (1 x 10(6) cfu/mL per kilogram) in 40 Wistar rats under sterile conditions. Forty rats with induced peritonitis were randomly divided into five groups: control, laparotomy, CO2 insufflation, N2O insufflation, and one group without pneumoperitoneum. Eight hours after the intraperitoneal injection of B. fragilis, peritoneal aspirates were obtained and inoculated onto Brucella agar. At the sixteenth hour of induced peritoneal infection (corresponding to hour 8 in the laparoscopy groups) all animals underwent laparotomy; peritoneal aspirates were obtained and inoculated into Brucella agar for bacterial counts. The colonies of B. fragilis were counted manually, and the results were expressed as the mean number of colony-forming units per milliliter. RESULTS: No significant differences in microorganism counts were noted between the study groups before the procedure (p>.05 for all comparisons). We observed a significant increase in the number of bacteria (mean +/- SD) in the CO2 insufflation group between hour 8 and hour 16 of peritoneal contamination. CONCLUSION: The results suggest that CO2 insufflation may promote the growth of intra-abdominal anaerobic bacteria. Such bacterial growth may lead to intra-abdominal abcess formation or cause localized peritonitis to develop into generalized peritonitis. We suggest that laparoscopy without pneumoperitoneum may be preferred in patients with peritonitis.     

Does laparoscopy increase bacteremia and endotoxemia in a peritonitis model?

Background: Laparoscopy is increasingly used in patients with intraabdominal bacterial infection although pneumoperitoneum may increase bacteremia by elevated intraabdominal pressure. Methods: The influence of laparotomy and laparoscopy on bacteremia, endotoxemia, and postoperative abscess formation was investigated in a rat model. Rats received intraperitoneally a standardized fecal inoculum and underwent laparotomy (n= 20), or laparoscopy (n= 20), or no further manipulation in the control group (n= 20). Results: Bacteremia and endotoxemia were higher after laparotomy and laparoscopy compared to the control group (p= 0.01) 1 h after intervention. One hour after intervention, aerobic and anaerobic bacterial species were detected in the laparotomy group while only anaerobic bacteria were found in the other two groups. Although bacteremia and endotoxemia did not differ among the three groups after 1 week, the mean number of intraperitoneal abscesses was significantly higher (p < 0.05) after laparotomy (n= 10) compared with laparoscopy (n= 6) and control group (n= 5). Conclusion: Laparoscopy does not increase bacteremia and intraperitoneal abscess formation compared to laparotomy in an animal model of peritonitis. Received: 28 May 1996/Accepted: 25 July 1996     

Effects of laparoscopy on intraperitoneal tumor growth and distant metastases in an animal model.

BACKGROUND AND AIMS: Laparoscopic surgery for colorectal cancer is currently being evaluated in humans. The aim of this study was to examine the effect of laparoscopy on intraperitoneal tumor growth and distant metastases in an animal model. We also examined the effect of combining laparotomy with laparoscopy and on infusing the peritoneal cavity with normal saline solution (NaCl), water, and sodium hypochlorite after laparoscopy on intraperitoneal tumor growth. MATERIAL AND METHODS: Female Fischer rats were given MtLn3 adenocarcinoma cells by intraperitoneal injection to produce intraperitoneal tumor growth and by tail vein injection to produce lung metastases. A pneumoperitoneum was then induced to a pressure of 8 mm Hg with carbon dioxide (CO2), helium, or room air. After this, animals were allowed to either recover or underwent laparotomy or infusion of NaCl, water, or sodium hypochlorite before recovery, depending on the experiment. At 21 days all animals were killed and intraperitoneal tumor growth was assessed by counting the number of peritoneal and serosal nodules and by weighing the omental pad of tumor. Lung metastases were assessed by counting the number of metastases after fixation. RESULTS: Laparoscopy caused a marked intraperitoneal dissemination of tumor with a median of 17 (10 to 20) peritoneal and serosal nodules for CO2, 19.5 (12.5 to 25) for helium, and 15.0 (9.5 to 17.7) for room air compared with 0 (0 to 1) for controls (P < .0001). The weight of omental tumor was also significantly increased (P < .02) in the CO2, helium, and room air groups. Infusion with NaCl, water, or sodium hypochlorite had no effect on tumor dissemination after laparoscopy. The combination of laparoscopy and laparotomy caused a significant reduction (P < .05) in the number of peritoneal nodules but had no significant effect on omental tumor growth. Laparoscopy also had no effect on the number of pulmonary metastases induced compared with controls. CONCLUSIONS: This study shows that laparoscopy promotes intraperitoneal dissemination of tumor. This effect is independent of the insufflating gas used and is not affected by use of a cytotoxic agent. The use of gasless laparoscopy should be encouraged by those undertaking curative laparoscopic surgery for colorectal cancer.     

Effect of CO2 pneumoperitoneum on the systemic and peritoneal cytokine response in a LPS-induced sepsis model

We studied the effect of carbon dioxide (CO2) pneumoperitoneum on the systemic and peritoneal cytokine response in a rat model of intraperitoneal sepsis. After intraperitoneal injection of bacterial lipopolysaccharide (LPS, 10 mg/kg), rats were divided into 3 groups (n = 49 in each group): control (abdominal puncture); CO2 pneumoperitoneum, and laparotomy. Blood and peritoneal lavage fluid (PLF) were sampled at 0, 1, 2, 3, 4, 6, and 8 h after LPS challenge. Blood cell counts, plasma endotoxin level, and the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) in the plasma and PLF were measured. Blood cell counts did not differ between the 3 groups. Plasma endotoxin levels in the pneumoperitoneum group were significantly increased immediately after the procedure (p < 0.05). Although peak plasma TNF-alpha levels in the pneumoperitoneum group were seen immediately after the procedure, other changes in plasma cytokine levels did not differ significantly between the 3 groups. PLF TNF-alpha and IL-1beta levels in the pneumoperitoneum group were significantly lower than levels in the control and laparotomy groups soon after the procedure (p < 0.05). PLF IL-6 levels in the pneumoperitoneum group tended to be lower than those in the laparotomy group. In conclusion, CO2 pneumoperitoneum might induce different responses between systemic and peritoneal cytokines soon after the procedure in a rat model of intraperitoneal sepsis.     

Influence of different gases and intraperitoneal instillation of antiadherent or cytotoxic agents on peritoneal tumor cell growth and implantation with laparoscopic surgery in a rat model

BACKGROUND: A generally accepted approach to prevent tumor implantation with laparoscopic surgery does not exist. Alternative gases in combination with intraperitoneal instillation of different antiadherent or cytotoxic agents have not been evaluated. METHODS: The effect of taurolidine, heparin, and povidone-iodine on the growth of colon adenocarcinoma DHD/K12/TRb was measured in rats undergoing laparoscopy with carbon dioxide (n = 40), helium (n = 40), or xenon (n = 40). In the procedure, 10(4) tumor cells were administered intraperitoneally, and pneumoperitoneum was established over 30 min at 8 mmHg with the different gases. The rats additionally received intraperitoneal instillation with one of the following: 1 ml of Ringer's solution, 1 ml of 0.5% taurolidine, 1 ml 0.5% taurolidine with heparin (10 U/ml), or 1 ml 0.25% of povidone-iodine. Tumor growth was measured after 4 weeks. RESULTS: Median intraperitoneal tumor weight was lower in rats receiving taurolidine (CO(2): 10 mg; helium: 50 mg; xenon: 39.5 mg) or taurolidine with heparin (CO(2): 4 mg; helium: 4.5 mg; xenon: 46.5 mg) in all gas groups than in the control groups (CO(2): 427 mg; helium: 268 mg; xenon: 345 mg) (p < 0.001). Whereas povidone-iodine caused significantly lower tumor growth in the CO(2) group (56.5 mg) (p < 0.01), the combination of helium (145 mg) and xenon (457 mg) with povidone-iodine produced no reduction of tumor growth as compared with the control groups (helium: 268 mg; xenon: 345 mg). CONCLUSIONS: Taurolidine and taurolidine with heparin significantly inhibit intraperitoneal tumor growth, with different gases used for pneumoperitoneum. Only povidone-iodine caused significant decrease of tumor growth in combination with CO(2). The combination of xenon and povidone-iodine should not be used in patients with cancer because of increased tumor growth.     

不同气腹介质对肿瘤细胞体外生长的影响

目的研究腹腔镜手术中不同气腹介质对肿瘤细胞体外生长的影响。方法采用3 H TdR掺入法 ,比较肿瘤细胞在经过“CO2 气腹”、“He气腹”、“Air气腹”条件后 ,肿瘤细胞摄取胸腺嘧啶核苷合成DNA(CPM值 )的情况。结果“气腹”后第 2 4hCO2 组CPM值较He组、Air组及对照组明显增高 (F =4 7 5 76 5 ,P <0 0 1) ,He组、Air组及对照组之间差异无显著性 (P >0 0 5 )。“气腹”后第 4 8h、72h、96hCO2 组较He组、Air组及对照组CPM值明显增高 (F =116 183,10 82 92 ,5 116 75 ,P <0 0 1) ,He组较Air组、对照组CPM值下降 (P <0 0 1) ,Air组与对照组之间差异无显著性 (P >0 0 5 )。结论CO2 可刺激肿瘤细胞生长 ,He可抑制肿瘤细胞生长。     

The influence of CO2 versus helium insufflation or the abdominal wall lifting technique on the systemic immune response

BACKGROUND: Both laparoscopic and conventional surgery result in activation of the systemic immune response; however, the influence of the laparoscopic approach, using CO2 insufflation, is significantly less. Little is known about the influence of alternative methods for performing laparoscopy, such as helium insufflation and the abdominal wall lifting technique (AWLT), and the systemic immune response. METHODS: Thirty-three patients scheduled for elective cholecystectomy were randomly assigned to undergo laparoscopy using either CO2 or helium for abdominal insufflation or laparoscopy using only the AWLT. The postoperative inflammatory response was assessed by measuring the white blood cell count, C-reactive protein (CRP) and interleukin-6 (IL-6). The postoperative immune response was assessed by measuring monocyte HLA-DR expression. RESULTS: CRP levels were significantly higher 1 day after helium insufflation when compared with CO2 insufflation; however, no differences were observed 2 days after surgery. The AWLT resulted in significantly higher levels of CRP both 1 and 2 days after surgery when compared with either CO2 or helium insufflation. A small increase in postoperative IL-6 levels was observed in all groups, but no significant differences were seen between the groups. After both helium insufflation and AWLT a significant decrease in HLA-DR expression was observed, in contrast to the CO2 group. CONCLUSION: Carbon dioxide used for abdominal insufflation seems to limit the postoperative inflammatory response and to preserve parameters reflecting the immune status. These findings may be of importance in determining the preferred method of laparoscopy in oncologic surgery.     

Effects of pneumoperitoneum on hemodynamic and systemic immunologic responses to peritonitis in pigs

BACKGROUND: Experimental evidence supporting the safety of laparoscopic intervention during sepsis is limited. The purpose of this study was to evaluate the effects of pneumoperitoneum on immunologic and hemodynamic responses to peritoneal sepsis. MATERIALS AND METHODS: A porcine model of peritonitis was created using an intraperitoneal autologous fecal inoculum. Pigs were then subjected to one of four procedures 24 h postinoculation (n = 6 per group): laparotomy, CO(2) laparoscopy, helium laparoscopy, and anesthesia only (1.5% isoflurane in 100% O(2), mechanical ventilation). Venous blood samples were obtained prior to inoculation, and at 24 (prior to procedure), 30, 48, 72, and 96 h postinoculation to determine white blood count (WBC) with differential, C-reactive protein (CRP), tumor necrosis factor, and bacteremia. Heart rate, end-tidal CO(2) (ETCO(2)), mean arterial blood pressure (MAP), and arterial blood gas variables were also measured at baseline and every 30 min throughout the procedure. RESULTS: Postoperative blood cultures confirmed systemic bacteremia in all groups at all time periods postinoculation. Following inoculation, WBC, band cell count, and CRP remained elevated above baseline in all groups throughout the study (P < 0.01). However, no significant differences in these parameters were observed among groups. In the CO(2) laparoscopy group, MAP, ETCO(2), and arterial pCO(2) were increased above baseline, while pH was decreased throughout the procedure (P < 0.01). CONCLUSIONS: In this animal model of peritonitis, CO(2) pneumoperitoneum induced hypercapnia, acidemia, and systemic hypertension intraoperatively, without a discernable effect on systemic immune function.     

Effect of laparotomy and laparoscopy on the establishment of lung metastasis in a murine model

BACKGROUND: Laparoscopic surgery is now applied to patients with gastrointestinal cancer. In animal studies, extraperitoneal tumor growth has been significantly less after laparoscopy than after laparotomy, but whether hematogenous metastasis occurs less frequently after laparoscopy is unknown. The aim of this study was to compare the frequency and growth of lung metastasis and serum levels of IL-6 and tumor necrosis factor-alpha (TNF-alpha) in mice treated by laparotomy and in mice treated by laparoscopy. METHODS: We used 182 male BALB/c mice. Colon 26 cancer cells (5 x 10(4)) were injected into the tail vein, and the mice were assigned to a laparotomy group (3-cm laparotomy), a laparoscopy group (carbon dioxide pneumoperitoneum at 6 to 8 mm Hg for 30 minutes), or a control group. Lung weight, number of lung metastases, and serum levels of IL-6 and TNF-alpha were measured and compared among the 3 groups. RESULTS: The lung weight and number of metastases on the lung surface and cut section in the laparotomy group (0.44+/-0.21 g, 55.7+/-46.7, 23.0+/-19.0) were significantly larger than those in the laparoscopy group (0.32+/-0.15 g, 29.9+/- 25.5, 13.1+/-9.9) or the control group (0.28+/-0.13, 29.3+/-26.2, 11.1+/-11.1). Three hours after the procedures, the serum level of IL-6 was significantly higher in the laparotomy group (1353 +/- 790 pg/mL) than in the laparoscopy group (671+/-353 pg/mL) or the control group (333+/-341 pg/mL). The lung weight, number of lung metastases, and levels of IL-6 and TNF-alpha were not different between the laparoscopy and control groups. CONCLUSIONS: Our results indicate that, although laparotomy accelerates tumor metastasis to the lung in this murine model, laparoscopy does not increase the frequency and growth of lung metastasis. The laparoscopic approach may suppress hematogenous metastasis to the lung because of decreased surgical stress and reduced cytokine response.     

Is helium insufflation superior to carbon dioxide insufflation in bacteremia and bacterial translocation with peritonitis?

PURPOSE: To evaluate the effects of CO2 or helium insufflation on bacteremia and bacterial translocation in rats with peritonitis. MATERIALS and METHODS: Forty male Wistar-Albino rats were divided into four groups, each containing 10 rats. The rats in the first group were injected only with E. coli into their peritoneal cavities with no further manipulation. The second group, following E. coli injection, underwent midline laparotomy without manipulation of the viscera for 1 hour. After the injection of E. coli in the third and fourth groups, CO2 and helium pneumoperitoneum, respectively, were maintained for 1 hour under 14 mm Hg pressure. At the end of the sixth hour, tissue samples were taken from the liver, spleen, lung, and mesenteric lymph nodes in order to evaluate bacterial translocation. During the study, blood samples were taken from each rat at 0, 1, 2, 4, and 6 hours to demonstrate bacteremia. RESULTS: There was a significant increase in bacteremia in the CO2 pneumoperitoneum group compared with the laparotomy-only and helium groups at 1 and 2 hours. Although all the blood samples at the fourth hour were positive for E. coli in every rat of all groups, helium was associated with a lower incidence of bacteremia at the sixth hour compared with other groups (P < 0.05). The CO2 pneumoperitoneum caused bacterial translocation to all organs from which tissue samples were taken. Although there was an insignificant decrease in translocation to the liver, spleen, and lung with helium compared with CO2 insufflation, helium did not increase bacterial translocation to the spleen compared with laparotomy alone, as did CO2 (P < 0.05). CONCLUSION: Helium might be an alternative to CO2 insufflation in patients with peritonitis if these results are confirmed by further experimental and clinical trials.     

Cardiopulmonary changes during laparoscopy and vessel injury: comparison of CO2 and helium in an animal model

BACKGROUND: Injury of venous vessels during elevated intraperitoneal pressure is thought to cause possible fatal gas embolism, and helium may be dangerous because of its low solubility. METHODS: Twenty pigs underwent laparoscopy with either CO2 (n=10) or helium (n=10) with a pressure of 15 mm Hg and standardized laceration (1 cm) of the vena cava inferior. After 30 s, the vena cava was clamped, closed endoscopically by a running suture and unclamped again. During the procedure changes of cardiac output (CO), heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP), end tidal CO2 pressure (PETCO2), and arterial blood gas analyses (pH, pO2 and pCO2) were investigated. RESULTS: No animal died during the experimental course (mean blood loss during laceration: CO2, 157+/-50 ml; helium, 173+/-83 ml). MAP and CO values showed a decrease after laceration of the vena cava in both groups that had already been completely compensated for before suturing. PETCO2 increased significantly after CO2 insufflation (P<0.01), while helium showed no effect. Laceration of the vena cava caused no significant changes in PETCO2 values in either group. Significant acidosis and an increase of pCO2 were only found in the CO2 group. CONCLUSIONS: The incidence of gas embolism during laparoscopy and accidental vessel injury seems to be very low. With the exception of acidosis and an increase of PETCO2 in the CO2 group, there were no differences in cardiopulmonary function between insufflation of CO2 and helium.     

New therapeutic strategies to avoid intra- and extraperitoneal metastases during laparoscopy: results of a tumor model in the rat

BACKGROUND: Therapeutic strategies to prevent port site recurrences in laparoscopy surgery of malignancies have not been investigated until now. METHODS: The effects of taurolidine, heparin, and povidone iodine on the growth of rat and human colon adenocarcinoma as well as gallbladder carcinoma were investigated in vitro. Furthermore, cytokine release of growth-stimulating IL-1beta by peritoneal macrophages was measured after incubation with carbon dioxide and additional incubation with the different agents. In the third experiment, prevention of intra- and extraperitoneal metastases by intraperitoneal instillation of the different agents during laparoscopy was investigated in a colon carcinoma model in the rat. Tumor cells were administered intraperitoneally in 100 rats, and pneumoperitoneum (8 mm Hg) was established over 30 min with carbon dioxide. Rats received either tumor cells, cells + heparin, cells + povidone iodine, cells + taurolidine, or cells + taurolidine + heparin. RESULTS: In vitro, tumor cell growth decreased after incubation with taurolidine, taurolidine/heparin, and povidone iodine. Cytokine release was stimulated by incubation with carbon dioxide and could only be suppressed by incubation with taurolidine in vitro. In vivo, intraperitoneal tumor weight was lower in rats receiving heparin (251 +/- 153 mg) and povidone iodine (134 +/- 117 mg) compared to the control group (541 +/- 291 mg), but even less when taurolidine (79 +/- 82 mg) or taurolidine/heparin (18.3 +/- 30 mg) were instilled. CONCLUSION: Heparin slightly inhibits intraperitoneal tumor growth in vivo, while povidone iodine and taurolidine cause a significant decrease in tumor cell growth in vitro as well as intraperitoneal tumor growth in vivo. Cytokine release of peritoneal macrophages is only suppressed by taurolidine. Total tumor take and trocar metastases are only suppressed by taurolidine and taurolidine/heparin. Copyright Copyright 1999 S. Karger AG, Basel     

Metabolic and immunologic consequences of laparoscopy with helium or carbon dioxide insufflation: a randomized clinical study

Background : Previous studies using animal models have demonstrated that carbon dioxide (CO₂) pneumoperitoneum during laparoscopy is associated with adverse physiological, metabolic, immunological and oncological effects, and many of these problems can be avoided by the use of helium insufflation. The present study was performed in patients to compare the effect of helium and CO₂ insufflation on intraperitoneal markers of immunological and metabolic function. Methods : Eighteen patients undergoing elective upper gastrointestinal laparoscopic surgery were randomized to have insufflation achieved by using either helium (n = 8) or CO₂ (n = 10) gas. Intraperitoneal pH was monitored continuously during surgery, and peritoneal macrophage function was determined by harvesting peritoneal macrophages at 5 min and 30 min after commencing laparoscopy, and then assessing their ability to produce tumour necrosis factor‐α (TNF‐α), and their phagocytic function. Results : Carbon dioxide laparoscopy was associated with a lower intraperitoneal pH at the commencement of laparoscopy, although this difference disappeared as surgery progressed. The production of TNF‐α was better preserved by CO₂ laparoscopy, but the insufflation gas used did not affect macrophage phagocytosis. Patients undergoing helium laparoscopy required less postoperative analgesia. Conclusion : The choice of insufflation gas can affect intraperitoneal macrophage function in the clinical setting, and possibly acid–base balance. The present study suggested no immunological advantages for the clinical use of helium as an insufflation gas. The outcomes of the present study, however, are different to those obtained from previous laboratory studies and further research is needed to confirm this outcome.     

Effectors of hypercarbia during experimental pneumoperitoneum.

Hypercarbia occurs during laparoscopy with carbon dioxide (CO2) insufflation. This may be due to increased ventilatory dead space after expansion of the peritoneal cavity with impairment of diaphragmatic excursion, or to increased absorption of CO2 from the peritoneum. To separate these effects, the authors examined the consequences of different insufflating gases and of diminished tissue perfusion on hypercarbia and dead space during pneumoperitoneum. Helium was chosen as an alternate insufflating gas because it is both inert and minimally absorbed. Eight swine (18 to 20 kg) were anesthetized, paralyzed, and mechanically ventilated at constant minute volume. Pneumoperitoneum with helium was maintained at 15 mm Hg for 45 minutes. After desufflation and stabilization for 1 hour, pneumoperitoneum was repeated with CO2. The sequence was again repeated after hemorrhagic shock to constant mean arterial pressure of 50 mm Hg. Data was analyzed by analysis of variance; significance levels are P < 0.01 unless otherwise listed. Arterial PCO2 increased significantly with CO2 insufflation within 15 minutes in normotensive animals and within 30 minutes during hypotension. Arterial pH decrease with CO2 pneumoperitoneum was significant in both groups at 30 minutes. Mixed venous PCO2 also increased with CO2 pneumoperitoneum within 30 minutes. Hypotension did not alter these changes. No significant changes were seen with helium pneumoperitoneum. Neither helium nor CO2 pneumoperitoneum significantly altered dead space. The authors make the following conclusions: 1) Absorption of CO2 from the abdomen during CO2 pneumoperitoneum produces respiratory acidosis, which is not seen with helium insufflation; 2) Pneumoperitoneum does not significantly increase dead space with either gas; 3) Transperitoneal absorption of CO2 is only partly related to perfusion because significant hypercarbia occurs during hemorrhagic shock.     

Impact of laparoscopic colonic resection on tumour growth and spread in an experimental model.

BACKGROUND: The influence of surgical manipulation and carbon dioxide pneumoperitoneum on intraperitoneal tumour growth and port-site metastasis during laparoscopic colon resection is still unknown. METHODS: Some 33 male WAG/Rij rats were randomized into three experimental groups: a laparoscopy group with carbon dioxide pneumoperitoneum (n = 11), a gasless laparoscopy group (n = 11) and a laparotomy group (n = 11). After transanal injection of a tumour cell suspension (1 x 106 CC 531 cells) into the distal colon, a colon segment resection and an end-to-end anastomosis (laparoscopy; intra-abdominal technique) were performed. Tumour growth was scored semiquantitatively 24 days after the operation. Data were analysed by the Kruskal-Wallis test. RESULTS: The tumour indices from the four locations with the greatest tumour growth were significantly decreased in the laparoscopy group with carbon dioxide pneumoperitoneum compared with the gasless laparoscopy and laparotomy groups (P < 0.01). Port-site metastases were significantly decreased in the carbon dioxide pneumoperitoneum group compared with the gasless laparoscopy group (P = 0.05). CONCLUSION: A full laparotomy incision promotes greater tumour growth than does carbon dioxide pneumoperitoneum. Surgical manipulation stimulates local tumour spread more than the establishment of a carbon dioxide pneumoperitoneum.     

Intraperitoneal hypothermia during surgery enhances postoperative tumor growth

BACKGROUND: Recent work has shown that intraoperative hypothermia is a significant source of surgical trauma, with wide-ranging physiological and immunological sequelae. The aim of this study was to examine the effects of intraperitoneal hypothermia during laparoscopy on tumor growth in an animal model. METHODS: Thirty WAG rats were randomized to undergo anesthesia alone (n = 10), insufflation with cold carbon dioxide (CO2) (n = 10), or insufflation with warm CO2 (n = 10). During insufflation, 1 x 105/ml CC531s colon cancer cells in suspension were injected into the peritoneal cavity. The control group was anesthetized and tumor cells were injected without insufflation. After 3 weeks, total tumor weight and the extent of tumor spread, as assessed by the modified Peritoneal Cancer Index (PCI), were compared at autopsy. RESULTS: Laparoscopy with cold CO2 resulted in a significant reduction in local and core body temperatures (p <0.05). Tumor growth in both groups that underwent CO2 pneumoperitoneum was significantly increased compared with the group that did not (p <0.0001, control vs warm CO2 and cold CO2). There was significantly more tumor growth in the rats insufflated with unwarmed CO2 than in the normothermic group (mean total tumor 0.01 g +/- 0.03 vs. 0.043 g +/- 0.07; p = 0.025 Mann-Whitney U test). Tumor spread as shown by the PCI scores was less in the warm gas group than it was in the animals insufflated with cold gas (151 vs 266). CONCLUSIONS: These data demonstrate that the peritoneal insufflation of CO2 enhances tumor growth and that the prevention of perioperative hypothermia during laparoscopy attenuates tumor growth. This effect may be partially mediated by the increased peritoneal trauma that results from insufflation with cold gas.     

Laparoscopic pneumoperitoneum in acute peritonitis does not increase bacteremia or aggravate metabolic or hemodynamic disturbances

The use of laparoscopy in generalized peritonitis has become increasingly frequent in recent years. However, CO2 pneumoperitoneum in association with increased intraperitoneal pressure may have deleterious effects in patients with hemodynamic or metabolic disturbances caused by bacterial peritonitis. The purpose of this study was to investigate the effect of CO2 pneumoperitoneum on bacteremia, mean arterial pressure, and blood gas disturbances in an animal model of bacterial peritonitis. Dogs were anesthetized, orally intubated, and subjected to experimental peritonitis by intraperitoneal inoculation of a suspension containing Escherichia coli and sterile dog feces. The animals were randomly assigned to two groups: control animals were maintained under anesthesia, and the insufflated animals were subjected to intraperitoneal CO2 insufflation. Bacterial peritonitis provoked the appearance of bacteremia and a significant decrease in mean arterial pressure, pH, bicarbonate, and base deficit. The induction of bacterial peritonitis did not significantly influence pH in the control group and partial pressure of arterial CO2 in either group. Thirty minutes of CO2 pneumoperitoneum did not influence the effect of bacterial peritonitis on the analyzed variables. These results suggest that laparoscopic CO2 pneumoperitoneum does not aggravate bacteremia or metabolic and hemodynamic disturbances induced by bacterial peritonitis.     

Intraperitoneal carbon dioxide insufflation and cardiopulmonary functions. Laparoscopic cholecystectomy in pigs.

We studied the effects of laparoscopic cholecystectomy on respiratory and hemodynamic function in eight adult pigs. Minute ventilation was adjusted to normalize baseline arterial blood gases, then fixed throughout carbon dioxide insufflation. A metabolic measurement cart recorded total CO2 excretion, oxygen consumption, and minute ventilation. Carbon dioxide pneumoperitoneum was maintained at a constant pressure of 15 mm Hg as cholecystectomy was performed. After 1 hour of insufflation, CO2 excretion increased from 115 +/- 10 mL/min to 149 +/- 9 mL/min but O2 consumption remained unchanged. The PaCO2 increased from 35 +/- 2 mm Hg to 49 +/- 3 mm Hg and arterial pH fell from 7.47 +/- 0.02 to 7.35 +/- 0.03. Systemic and pulmonary hypertension occurred and stroke volume dropped from 35.5 +/- 3.5 mL to 28.6 +/- 2.2 mL with compensatory tachycardia. Right atrial pressure remained unchanged as inferior vena cava pressure increased to reflect the intraperitoneal pressure. We conclude that CO2 pneumoperitoneum resulted in significant transperitoneal CO2 absorption, with secondary hypercapnia and acidemia. The accumulation of CO2 was also associated with an increase in systemic and pulmonary arterial pressure. Heart rate increased to compensate for the decreased stroke volume to maintain cardiac output.     

Carbon dioxide pneumoperitoneum-mediated attenuation of the inflammatory response is independent of systemic acidosis

BACKGROUND: The purpose of this study was to determine if systemic acidosis induced by peritoneal absorption of carbon dioxide (CO2 ) during laparoscopy plays a role in CO2 pneumoperitoneum-mediated attenuation of the acute phase inflammatory response associated with perioperative sepsis. The influence of hepatic polymorphonuclear (PMN) leukocyte infiltration on this phenomenon was also investigated. METHODS: Forty-five rats were randomized into 5 groups: anesthesia control, open cecal ligation and puncture (OCLP), laparoscopic cecal ligation and puncture using helium for insufflation (He LCLP), LCLP using CO2 with continued spontaneous ventilation (LCLP-SV), and LCLP using CO2 with intubation and positive pressure ventilation (LCLP-PPV). RESULTS: After 30 minutes, arterial blood gas parameters remained normal in control, OCLP rats, and He LCLP rats, while CO2 LCLP-SV rats developed significant hypercarbic acidosis. This acidosis was corrected in CO2 LCLP-PPV rats ( P < .0001 vs CO2 LCLP-SV for both). Expression of the rat acute phase gene alpha 2 -macroglobulin was greater after OCLP and He LCLP than after either CO2 LCLP-SV or CO2 LCLP-PPV ( P < .0001 vs either CO2 OCLP-SV for both). However, levels of alpha 2 -macroglobulin were not significantly different between the acidotic (LCLP-SV) and normocarbic (LCLP-PPV) CO2 groups. Infiltration of the hepatic parenchyma by PMNs did not differ significantly between groups. CONCLUSIONS: CO2 insufflation-induced systemic acidosis is not responsible for the reduction in the acute phase inflammatory response observed in laparoscopic animal models of sepsis. Hepatic PMN infiltration also does not appear to mediate this effect.     

Influence of different gases used for laparoscopy (helium, carbon dioxide, room air, and xenon) on tumor volume, histomorphology, and leukocyte–tumor–endothelium interaction in intravital microscopy

Background Previouse studies indicate that helium pneumoperitoneum used for laparoscopic surgery suppresses whereas carbon dioxide pneumoperitoneum increases postoperative tumor growth. The pathomechanisms of decreased tumor growth by helium are unknown. This study was designed to examine the effect of the gases helium, carbon dioxide (CO₂), and air, and xenon, which can be used to induce pneumoperitoneum in laparoscopy on tumor volume, histomorphology, and leukocyte–endothelium interaction measured by intravital microscopy in rats with implanted liver malignoma (Morris hepatoma 3924A).Methods In 46 rats, Morris hepatoma 3294A cells were implanted intrahepatically. After implantation, rats were randomized into two main groups. In the first main group, 10 animals were prepared for examination of leukocyte–endothelium interaction by intravital video microscopy and were randomized into two groups. Five days after implantation they underwent laparoscopy using either helium (n = 5) or CO₂ (n = 5). Ten days after implantation the rats underwent intravital video microscopy to assess leukocyte–endothelium interaction in the tumor and liver vessels. In the second main group 36 rats were prepared for examination of tumor volume arid histomorphology. They were randomized into five groups. Five days after implantation they underwent laparoscopy using helium (n = 7), carbon dioxide (n = 7), room air (n = 7), or xenon (n = 8). The control group (n = 7) received anesthesia only. Rats were killed 10 days after tumor implantation to assess tumor volume and histomorphology.Results Compared to the control group or groups that received CO₂, room air, or xenon for pneumoperitoneum, the establishment of helium pneumoperitoneum caused a significantly smaller tumor volume (Kruskal-Wallis test, p = 0.001; median tumor-volume: control group, 44 mm³; helium 19 mm³). There was no significant difference in histomorphology between the groups. There was only a statistically significant difference in the development of central tumor necrosis in accordance to tumor volume (Mann-Whitney test, p = 0.03). In the tumor samples, roller counts were statistically significantly higher in the helium group compared to the CO₂ group (p = 0.04). For sticker counts, no statistically significant effects due to liver/tumor (p = 0.13) or treatment (p = 0.48) were observed.Conclusions There was a significant decrease in tumor volume using helium pneumoperitoneum for laparoscopy compared to the other gases. Here, we demonstrate that suppression of tumor growth is not due to variation of histomorphology. It seems that helium pneumoperitoneum effects a higher leukocyte–endothelium interaction and thereby a higher immune activation. This could be one explanation for the statistically significantly smaller tumor volume after laparoscopy with helium compared to laparoscopy with CO₂.