Combined Low Pressure Pneumoperitoneum and Intraperitoneal Infusion of Normal Saline for Reducing Shoulder Tip Pain Following Laparoscopic Cholecystectomy

Introduction Intraabdominal CO₂ gas after laparoscopic cholecystectomy causes postoperative shoulder-tip pain. Many methods of analgesia have been used to reduce this pain, including analgesic drugs, intraperitoneal local anesthetic, intraperitoneal saline, a gas drain, heated gas, low-pressure gas, and nitrous oxide pneumoperitoneum. The aim of this study was to evaluate the efficacy of combined low-pressure CO₂ pneumoperitoneum and intraperitoneal infusion of normal saline in reducing the incidence of postoperative shoulder-tip pain. Methods Altogether, 109 patients undergoing elective laparoscopic cholecystectomy were randomized prospectively into three groups. Patients in group A (n = 34) underwent laparoscopic cholecystectomy with 14 mmHg CO₂ pneumoperitoneum; patients in group B (n = 37) underwent laparoscopic cholecystectomy with 10 mmHg CO₂ pneumoperitoneum; and those in group C (n = 38) underwent laparoscopic cholecystectomy with 10 mmHg CO₂ pneumoperitoneum in addition to intraperitoneal normal saline infusion in the right hemidiaphragmatic area. Shoulder-tip pain was recorded on a verbal rating scale 2, 6, 12, 24, and 48 hours after operation. Results Twelve patients in group A (35.2 percent), six in group B (16.2 percent), and seven in group C (18.4 percent) complained of shoulder-tip pain. Hence, there was a significant decrease in the frequency of shoulder-tip pain in groups B and C in relation to group A, but there was no significant difference between groups B and C. The postoperative shoulder-tip pain scores were significantly reduced in group C at 6, 12, and 24 hours. The number of patients who required additional analgesics was also reduced in group C. Conclusions Low-pressure CO₂ pneumoperitoneum reduces the number of patients complaining of shoulder-tip pain and the intensity of the pain after laparoscopic cholecystectomy. The addition of intraperitoneal normal saline infusion to low-pressure CO₂ pneumoperitoneum seems to reduce the intensity but not the frequency of shoulder-tip pain after laparoscopic cholecystectomy.     

Effects of different pressure levels of CO2 pneumoperitoneum on liver regeneration after liver resection in a rat model

Background

A recent study demonstrated that high pressure of carbon dioxide (CO₂) pneumoperitoneum before liver resection impairs postoperative liver regeneration. This study was aimed to investigate effects of varying insufflation pressures of CO₂ pneumoperitoneum on liver regeneration using a rat model.

Methods

180 male Wistar rats were randomly divided into three groups: control group (without preoperative pneumoperitoneum), low-pressure group (with preoperative pneumoperitoneum at 5 mmHg), and high-pressure group (with preoperative pneumoperitoneum at 10 mmHg). After pneumoperitoneum, all rats were subjected to 70 % partial hepatic resection and then euthanized at 0 min, 12 h, and on postoperative days (PODs) 1, 2, 4, and 7. Following outcome parameters were used: liver regeneration (liver regeneration rate, mitotic count, Ki-67 labeling index), hepatocellular damage (serum aminotransferases), oxidative stress [serum malondialdehyde (MDA)], interleukin-6 (IL-6), and hepatocyte growth factor (HGF) expression in the liver tissue.

Results

No significant differences were observed for all parameters between control and low-pressure groups. The liver regeneration rate and mitotic count were significantly decreased in the high-pressure group than in control and low-pressure groups on PODs 2 and 4. Postoperative hepatocellular damage was significantly greater in the high-pressure group on PODs 1, 2, 4, and 7 compared with control and/or low-pressure groups. Serum MDA levels were significantly higher in the high-pressure group on PODs 1 and 2, and serum IL-6 levels were significantly higher in the high-pressure group at 12 h and on POD 1, compared with control and/or low-pressure groups. The HGF tissue expression was significantly lower in the high-pressure group at 12 h and on PODs 1 and 4, compared with that in control and/or low-pressure groups.

Conclusions

High-pressure pneumoperitoneum before 70 % liver resection impairs postoperative liver regeneration, but low-pressure pneumoperitoneum has no adverse effects. This study suggests that following laparoscopic liver resection using appropriate pneumoperitoneum pressure, no impairment of liver regeneration occurs.     

Laparoscopic surgery induced interleukin-6 levels in serum and gut mucosa: implications of peritoneum integrity and gas factors

Background  The peritoneum serves as an integral part of host immunity, and the homeostasis of intraperitoneal environment is held to be beneficial for patient recovery after abdominal surgery. How minimal invasive access to the abdomen by laparoscopy and incisions would alter the intraperitoneal immune response is not fully defined. This study examined the levels of IL-6 in serum and gut mucosa following laparoscopic surgery with reference to the peritoneum integrity and gas factors. Methods  BALB/c mice were divided into three groups (ten animals in each group) that underwent different abdominal surgical treatments: laparotomy (open group), laparoscopy with atmospheric air (air group) or carbon dioxide pneumoperitoneum (CO₂ group). A 3-cm incision of the skin and muscle was made in all animals except the peritoneum was left intact in the latter two animal groups in order to cancel out the incisional tissue injury present in laparotomy. Four hours after surgery, serum, and jejunal mucosa were extracted for IL-6 measurement by enzyme-linked immunosorbent assay (ELISA). Results  Open laparotomy resulted in significant elevation of serum IL-6 level when compared to the laparoscopic procedures in the descending order of open > air > CO₂ groups. For the mucosal IL-6 level, both the open and air groups were significantly higher than the CO₂ group. Data from multivariate analysis revealed that breaching or incision of the peritoneum was an important factor for the elevated levels of IL-6 in serum (p < 0.001) and jejunal mucosa (p = 0.032). Conclusion  The present study suggests that laparoscopic techniques to minimize the size of the peritoneal incision as well as exposure to atmospheric air can potentially reduce postoperative stress responses associated with abdominal surgery and prompt early recovery.     

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     

CO<Subscript>2</Subscript> pneumoperitoneum increases systemic but not local tumor spread after intraperitoneal murine neuroblastoma spillage in mice

Background  Minimally invasive techniques are increasingly used for biopsy and resection of neuroblastoma, but the impact on the behavior of spilled tumor cells is unknown. We aimed to investigate whether CO₂ pneumoperitoneum can affect local or systemic tumor manifestation after spillage of neuroblastoma cells into the peritoneal cavity. Methods  Murine neuroblastoma cells (Neuro2a, 1x10⁶) were inoculated into the peritoneal cavity of 25 male A/J mice, which subsequently underwent CO₂ pneumoperitoneum (n = 12) or laparotomy (n = 13) for 1 h. At the 28th postoperative day, local (peritoneal and surface of the gut) and systemic (liver, lung, spine) tumor spread was graded in a blinded manner (1–4 point scale) and specimens were histologically examined for tumor manifestation (hematoxylin and eosin stain) and tumor cell proliferation rate (Ki-67-stain). In the case of no visible lesion, five random sections were histologically examined. Peritoneal carcinosis was graded macroscopically. Results  Tumor manifestations were detected in 10 out of 12 (83%) animals after CO₂ pneumoperitoneum, and in 9 out of 13 (69%) after laparotomy (n.s.). Incidence of liver metastasis was higher after CO₂ pneumoperitoneum versus laparotomy (83% versus 31%; p < 0.05). Incidence and grading of peritoneal carcinosis was not significantly different between the groups (n.s.). Intrapulmonary metastasis was found in one mouse of each group, but no metastasis of the spine. However, the grading of liver metastasis was higher after CO₂ pneumoperitoneum compared to laparotomy (p < 0.05). Tumor cell proliferation (Ki-67 stain) in the liver did not differ between both groups. Moreover, proliferation always exceeded 50% of tumor cells, irrespective local or systemic tumor manifestation. Conclusions  CO₂ pneumoperitoneum increased intrahepatic metastasis, but not local peritoneal carcinosis in a murine neuroblastoma model. This suggests that laparoscopy could promote systemic dissemination of intraperitoneally spilled tumor cells when no chemotherapy is applied. It remains to be determined whether this is due to local immune suppression or direct modulation of tumor cell behavior.     

The effect of timing of pneumoperitoneum on the inflammatory response

Background We examined the effects of an identical period of pneumoperitoneum applied at three different time points after lipopolysaccharide (LPS) challenge. Two different insufflation gases were also compared. Methods Male rats (n = 70) were injected intravenously with 1 mg/kg of LPS (time 0). The time relationship between a 1.5-h period of insufflation and initial LPS stimulation was the experimental variable. All rats were killed 6 h after injection. CO₂ and helium insufflation were investigated. Ten control rats received LPS only. Serum interleukin-6 (IL-6) levels were determined by enzyme-linked immunosorbent assay (ELISA). Hepatic expression of α₂-macroglobulin, β-fibrinogen, and metallothionein were measured by Northern blot analysis. Statistical analysis was performed using one-way analysis of variance (ANOVA). Results Expression of α₂-macroglobulin mRNA was lower in CO₂ groups compared to the control group (p < 0.05 at time 120 and 270). β-Fibrinogen message was diminished in CO₂ 0 and 120 groups compared to control. Serum levels of IL-6 and expression of metallothionein mRNA did not show significant differences between groups. Conclusions These findings suggest that CO₂ pneumoperitoneum downregulates the inflammatory response to LPS challenge. Start time of CO₂ insufflation does not appear to alter hepatic expression of acute phase genes. The mechanism of α₂-macroglobulin downregulation does not appear to be due to IL-6.     

Effect of different intra-abdominal pressure levels on QT dispersion in patients undergoing laparoscopic cholecystectomy

Background

Hemodynamic changes caused by carbon dioxide (CO₂) insufflation occur frequently in patients who undergo laparoscopic surgery. One indicator of these changes is corrected QT dispersion (QTcd), an index of myocardial function. Prolongation of QTcd has been associated with cardiovascular morbidity and mortality. We compared the effects of high-pressure (15 mmHg) and low-pressure (7 mmHg) CO₂ pneumoperitoneums on the QT interval, the rate-corrected QT interval (QTc), the QT dispersion (QTd), and the corrected QT dispersion (QTcd) during laparoscopic cholecystectomy.

Methods

Twenty consecutive patients were in a low-pressure pneumoperitoneum group and 32 were in a high-pressure pneumoperitoneum group. A 12-lead electrocardiogram was used to monitor cardiac variables. In all patients, serial electrocardiograms were recorded before anesthesia induction (baseline), immediately after the pneumoperitoneum had been created, every 15 minutes during CO₂ insufflation, and 5 minutes after deflation. Two observers measured the QT intervals independently, and the QTcd was calculated using Bazett’s formula.

Results

The QT interval and the QTc interval did not change significantly during the study in either group. The QTd and QTcd in the high-pressure pneumoperitoneum group increased significantly during CO₂ insufflation and were significantly higher in the high-pressure pneumoperitoneum group compared with the low-pressure pneumoperitoneum group. Changes caused by CO₂ insufflation were reversible.

Conclusions

Statistically significant increases of QTd and QTcd, which are associated with an increased risk of arrhythmias and cardiac events, occur during CO₂ insufflation in both high-pressure and low-pressure pneumoperitoneums. QTd and QTcd were significantly higher in the high-pressure pneumoperitoneum group than they were in the low-pressure pneumoperitoneum group. QT interval changes were not related to anesthetic agents, surgical stress, hypercapnia, or duration of CO₂ insufflation. Increased intra-abdominal pressure may have caused these changes.     

Endostatin Affects Osteoblast Behavior In Vitro,but Collagen XVIII/Endostatin Is Not Essential for Skeletal Development In Vivo

Endostatin, a fragment of collagen XVIII, can inhibit vascular endothelial growth factor (VEGF) signaling. VEGF is known to be crucial for bone development. The aims of this study were to investigate the influences of endostatin on osteoblast behavior in vitro and the roles of collagen XVIII/endostatin on bone development in vivo. For the in vitro experiments, MC3T3-E1 osteoblasts were treated with VEGF-A, 2 μg/ml endostatin, 20 μg/ml endostatin, VEGF-A + 2 μg/ml endostatin, or VEGF-A + 20 μg/ml endostatin. Osteoblast proliferation and matrix mineralization were analyzed. Faxitron, pQCT, and histological analyses were performed on hindleg bones of transgenic mice overexpressing endostatin (ES-tg) and mice lacking collagen XVIII (Col18a1 ^−/−) to study bone development in vivo. Treatment of cells with endostatin decreased osteoblast proliferation. Moreover, VEGF-A together with endostatin (2 μg/ml) decreased osteoblast proliferation and matrix mineralization. In vivo, Col18a1 ^−/− and ES-tg mice displayed no differences in bone density or mineral content during bone development, but ES-tg bones grew in length more slowly compared to the controls. The formation of secondary ossification centers was delayed in Col18a1 ^−/− mice. Immunohistochemistry revealed collagen XVIII in basement membranes of periosteal and bone marrow vessels and at muscle attachment sites. In conclusion, endostatin affects osteoblast behavior in vitro, the effects being boosted by simultaneous treatment with VEGF. In vivo, Col18a1 ^−/− and ES-tg mice show mild delays in bone development. These changes are transitory and suggest that collagen XVIII/endostatin does not play an indispensable role in skeletal development.     

The effect of pentoxifylline on oxidative stress in CO2 pneumoperitoneum

Background  Carbon dioxide (CO₂) pneumoperitoneum induces peritoneal oxidative stress. This experimental, randomized, controlled study was designed to investigate the effect of pentoxifylline on oxidative stress induced by CO₂ pneumoperitoneum. Methods  For this study, 36 Swiss albino rats were randomized into three groups. Arteria, vena femoralis, and peritoneal cavity were cannulated after anesthesia. The arterial pH, partial arterial oxygen pressure (PaO₂), venous PO₂, arterial and venous PO₂ difference (P_(a-v)O₂), serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and thiobarbituric acid-reactive substances (TBARS) were studied at the end of the first and second hours in group 1 (control). In group 2, 1 cc isotonic NaCl was injected into peritoneal cavity and then CO₂ pneumoperitoneum was established. At the end of the first hour of insufflation and one hour after desufflation, the same parameters as in group 1 were studied. In group 3, the CO₂ pneumoperitoneum plus pentoxifylline group, all procedures as in group 2 were repeated, with the exception of pentoxifylline (50 mg/kg) injected in place of saline. Results  At the end of the first hour, P_(a-v)O₂ value in group 2 was significantly less than in the control group (group 1) and group 3 (p < 0.05). There were no significant differences in PaO_2, pH, AST, and ALT values between groups (p > 0.05). TBARS level in group 1 was significantly lower than in the other groups, but there was no significant difference in TBARS level between groups 2 and 3. At the end of the second hour, TBARS level in group 3 was significantly lower than in group 2 (p < 0.05). Conclusions  Pentoxifylline may reduce the oxidative injury following laparoscopic procedures.     

Influence of carbon dioxide pneumoperitoneum environment on adhesion and metastasis of a human ovarian cancer cell line

Background  This study aimed to explore the adhesion and metastasis capability of the human ovarian cancer cell line SKOV₃ after exposure to a simulated laparoscopic carbon dioxide (CO₂) pneumoperitoneum environment and the related mechanism. Methods  SKOV₃ was subjected to a simulated laparoscopic CO₂ pneumoperitoneum environment at various CO₂ pressures (8–12 mmHg) and exposure times (1–3 h). Cell adhesive capacity was determined by a mechanical method. Real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) and immunocytochemical staining were used to examine the mRNA and protein expressions of heparanase (HPSE) and vascular endothelial growth factor C (VEGF-C) in SKOV₃. Cells cultured in a standard environment were used as the control. Results  The increase of SKOV₃ cell adhesion capability was associated with CO₂ pressure and exposure time. A significantly higher adhesion capability was observed in the group with exposure to 10 mmHg for 2 h over a 48 h period, as compared with the control groups (p < 0.05). The expressions of HPSE and VEGF-C in SKOV₃, which are closely related to metastasis capability, also increased. Significantly higher expressions were observed in the group with exposure to 10 mmHg for 3 h over a 48 h period, as compared with the control groups (p < 0.01). Conclusions  The adhesion and metastasis capacity of SKOV₃ increased with overexpression of HPSE and VEGF-C and were positively related to CO₂ pressure, exposure, and culture time.     

Correlation of CO2 pneumoperitoneal pressures between rodents and humans

Introduction  Many studies have reported on the effects of pneumoperitoneum in a rat model, using a wide range of intra-abdominal pressures. The correlation between pneumoperitoneal pressures in rodents to pressures in humans has not been established. This study evaluates changes in various physiological parameters in different pneumoperitoneum pressures in the rat model with a comparison to known data in humans. Materials and methods  Three groups of eight Wistar rats each were anesthetized, tracheostomized, and mechanically ventilated with fixed tidal volume and respiratory rate. After a stabilization phase, CO₂ pneumoperitoneum was established to 12, 8, and 5 mmHg in the different groups. Changes in blood pressure, heart rate, peak ventilatory pressure, and end-tidal CO₂ (ETCO₂) were recorded throughout the experiment. Results  There were no significant changes in blood pressure and heart rate in all groups. No increase in ETCO₂ was demonstrated following induction of pneumoperitoneum in the 12 and 8 mmHg groups. A statistical significant increase in ETCO₂ occurred only in the 5 mmHg group (39.4 to 41.3 mmHg, p = 0.023). Ventilatory pressures increased after induction of pneumoperitoneum in all groups. The increase reached a maximal level in the 8 and 12 mmHg groups (from 3 to 12 mmHg) and was lower in the 5 mmHg group (from 3 to 7 mmHg) Conclusions  The neglected increase in ETCO₂ in pressures ≥8 mmHg, in the rat correlates to high pressures in humans (above 14–20 mmHg) when CO₂ diffusion through the peritoneum declines due to pressure occlusion of peritoneal capillaries. The maximal ventilatory pressures generated in the rat in intra-abdominal pressures ≥8 mmHg correlate to pressures, which are higher than the standard working pressures in humans. Thus, pneumoperitoneal pressures >8 mmHg in the rat do not simulate routine working pressures employed in humans. A pressure of 5 mmHg is optimal in a rat model to simulate laparoscopy in humans.     

Influence of depth of neuromuscular blockade on surgical conditions during low-pressure pneumoperitoneum laparoscopic cholecystectomy: A randomized blinded study

Study objectiveTo evaluate the influence of neuromuscular blockade (NMB) on surgical conditions during low-pressure pneumoperitoneum (8 mm Hg) laparoscopic cholecystectomy (LC), while comparing moderate and deep NMB. Secondary objective was to evaluate if surgical conditions during low-pressure pneumoperitoneum LC performed with deep NMB could be comparable to those provided during standard-pressure pneumoperitoneum (12 mm Hg) LC.DesignProspective, randomized, blinded clinical trial.SettingOperating room.PatientsNinety ASA 1–2 patients scheduled for elective LC.InterventionsPatients were allocated into 3 groups: Group 1: low-pressure pneumoperitoneum with moderate-NMB (1–3 TOF), Group 2: low-pressure pneumoperitoneum with deep-NMB (1–5 PTC) and Group 3: standard pneumoperitoneum (12 mm Hg). Rocuronium was used to induce NMB and acceleromiography was used for NMB monitoring (TOF-Watch-SX).MeasurementsThree experienced surgeons evaluated surgical conditions using a four-step scale at three time-points: surgical field exposure, dissection of the gallbladder and extraction/closure.Main resultsLow-pressure pneumoperitoneum (Group 1 vs. 2): good conditions: 96.7 vs. 96.7%, 90 vs. 80% and 89.6 vs. 92.3%, respectively for the time-points, p > 0.05. No differences in optimal surgical conditions were observed between the groups. Surgery completion at 8 mm Hg pneumoperitoneum: 96.7 vs. 86.7%, p = 0.353.Standard-pressure pneumoperitoneum vs. low-pressure pneumoperitoneum with deep NMB (Group 3 vs. 2): good conditions: 100% in Group 3 for the three time-points (p = 0.024 vs. Group 2 at dissection of the gallbladder). Significantly greater percentage of optimal conditions during standard-pressure pneumoperitoneum LC at the three time points of evaluation.ConclusionsThe depth of NMB was found not to be decisive neither in the improvement of surgical conditions nor in the completion of low-pressure pneumoperitoneum LC performed by experienced surgeons. Surgical conditions were considered better with a standard-pressure pneumoperitoneum, regardless of the depth of NMB, than during low-pressure pneumoperitoneum with deep NMB.     

Lactate metabolism during laparoscopic cholecystectomy: comparison between CO2 pneumoperitoneum and abdominal wall retraction

Recent reports have implicated CO₂ pneumoperitoneum for laparoscopic surgery in the occurrence of postoperative mesenteric ischemia. With this kind of surgery, the increase in blood lactate levels has been attributed to anaerobic metabolism, probably due to tissue ischemia induced by high intraabdominal pressure (IAP). The aim of this study was to evaluate the metabolic repercussion of CO₂ pneumoperitoneum during laparoscopic cholecystectomy (LC). This was a prospective randomized study of CO₂ pneumoperitoneum (PP group, n= 19) versus abdominal wall retraction (AWR group, n= 15). Demographic data were collected preoperatively. Four-trocar LC was performed with either a CO₂ pneumoperitoneum (IAP of 12 mmHg) or abdominal wall retraction (abdominal wall pressure 6–10 kp). Intraoperative and postoperative blood samples were collected and lactate levels determined by enzymatic analysis. Repeated measures analysis of variance (MANOVA) was used for statistical analysis. Significance was evaluated at p < 0.05. The groups were shown to be homogeneous. Lactate concentration, expressed as mean (SD), went from 25.4 (14.4) mg/dl at baseline to 18.9 (13.6) mg/dl 4 hours after surgery in the PP group and from 19.4 (6.1) mg/dl at baseline to 17.8 (14.7) mg/dl in the AWR group. No significant differences were found between groups intraoperatively (p= 0.116) or postoperatively (p= 0.99). Our study did not show significant differences in blood lactate levels during LC with CO₂ pneumoperitoneum compared to the same procedure with abdominal wall retraction.     

Laparoscopic surgery and the parasympathetic nervous system

Background Laparoscopic surgery preserves the immune system and has anti-inflammatory properties. CO₂ pneumoperitoneum attenuates lipopolysaccharide (LPS)-induced cytokine production and increases survival. We tested the hypothesis that CO₂ pneumoperitoneum mediates its immunomodulatory properties via stimulation of the cholinergic pathway. Methods In the first experiment, rats (n = 68) received atropine 1 mg/kg or saline injection 10 min prior to LPS injection and were randomization into four 30-min treatment subgroups: LPS only control, anesthesia control, CO₂ pneumoperitoneum, and helium pneumoperitoneum. In a second experiment, rats (n = 40) received atropine 2 mg/kg or saline 10 min prior to randomization into the same four subgroups described previously. In a third experiment, rats (n = 96) received atropine 2 mg/kg or saline 10 min prior to randomization into eight 30-min treatment subgroups followed by LPS injection: LPS only control; anesthesia control; and CO₂ or helium pneumoperitoneum at 4, 8, and 12 mmHg. In a fourth experiment, rats (n = 58) were subjected to bilateral subdiaphragmatic truncal vagotomy or sham operation. Two weeks postoperatively, animals were randomized into four 30-min treatment subgroups followed by LPS injection: LPS only control, anesthesia control, CO₂ pneumoperitoneum, and helium pneumoperitoneum. Blood samples were collected from all animals 1.5 h after LPS injection, and cytokine levels were determined by enzyme-linked immunosorbent assay. Results Serum tumor necrosis factor-α (TNF-α) levels were consistently suppressed among the saline–CO₂ pneumoperitoneum groups compared to saline–LPS only control groups (p < 0.05 for all four experiments). All chemically vagotomized animals had significantly reduced TNF-α levels compared to their saline-treated counterparts (p < 0.05 for all), except among the CO₂ pneumoperitoneum-treated animals. Increasing insufflation pressure with helium eliminated differences (p < 0.05) in TNF-α production between saline- and atropine-treated groups but had no effect among CO₂ pneumoperitoneum-treated animals. Finally, vagotomy (whether chemical or surgical) independently decreased LPS-stimulated TNF-α production in all four experiments. Conclusion CO₂ pneumoperitoneum modulates the immune system independent of the vagus nerve and the cholinergic pathway. Paper presented at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), Fort Lauderdale, Florida, USA, April 2005     

Liver metastasis and ICAM-1 mRNA expression in the liver after carbon dioxide pneumoperitoneum in a murine model

Background Liver metastasis of colorectal malignancies is an important prognostic factor. Several studies have demonstrated that carbon dioxide (CO₂) pneumoperitoneum enhances liver metastasis in animal models. Little is known about intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha (TNF-(α) mRNA expression in the liver after CO₂ pneumoperitoneum. Methods Forty-five male BALB/c mice were randomly divided into three groups after intra-splenic tumor cell (colon 26) inoculation and the following procedures were performed: CO₂ pneumoperitoneum (n = 15), open laparotomy (n = 15), and anesthesia alone (n = 15). On day 7 after each procedure, the livers were excised and the number and diameter of the tumor nodules and the cancer index score were determined. Another 90 male BALB/c mice were randomly divided into three groups as described above, and they underwent each procedure (n = 30 each). After each procedure, the livers were excised on days 0, 1, 3, and ICAM-1 and TNF-α mRNA expression were examined by real-time RT-PCR using SYBR Green I. Results The number of tumor nodules and the cancer index score were larger in the CO₂ pneumoperitoneum group than in the control group (p < 0.05). The mean diameter of the tumor nodules was not different among the three groups. The expression of ICAM-1 in the CO₂ pneumoperitoneum group was higher than that in the other groups on day 1 (p < 0.05), and the TNF-α mRNA was higher than that in the control group on day 1 (p < 0.05). Conclusions CO₂ pneumoperitoneum enhances liver metastasis compared with anesthesia alone, and ICAM-1 expression in the liver after the pneumoperitoneum plays an important role in establishing liver metastasis in a murine model.     

Alterations in portal vein blood pH, hepatic functions, and hepatic histology in a porcine carbon dioxide pneumoperitoneum model

Background  

Intra-abdominal high pressure and acidosis by carbon dioxide (CO₂) pneumoperitoneum is known to affect various organ functions. In this study, changes in liver functions and liver histology were investigated during CO₂ pneumoperitoneum in a large animal model.     

A randomized controlled study evaluating the effects of the temperature of insufflated CO<Subscript>2</Subscript> on core body temperature and blood gases (an experimental study)

Background Heated carbon dioxide (CO₂) was used for pneumoperitoneum (Pp) to prevent hypothermia. This study aimed to investigate the relationship between the temperature of the insufflated CO₂ and blood gases together with the core body temperature (CBT). Methods A prospective controlled study was performed with 24 pigs weighing approximately 20 kg randomized into four groups of 6 pigs each. A pneumoperitoneum at 12 mmHg of pressure was applied for 60 min with the pig under general anesthesia. The CO₂ temperature was 22°C in group 1, 37°C in group 2, and 7°C in group 3. In the “sham” group, pneumoperitoneum was not applied. Arterial blood pH and partial pressure of CO₂ (PaCO₂) were analyzed before insufflation, every 15 min during the pneumoperitoneum, and 15 min after the desufflation. The CBT was recorded before the insufflation, every 20 min during pneumoperitoneum, and 20 min after the desufflation. Blood gas analyses and CBT records for the “sham” group were performed at the same intervals. Results Arterial blood pH gradually decreased during pneumoperitoneum. At the 60th minute of pneumoperitoneum, a minimum decrease in arterial blood pH (0.04; p = 0.027) and a minimum increase in PaCO₂ (3.67; p = 0.027) were recorded in group 3, whereas a maximum decrease in arterial blood pH (0.18; p = 0.027) and a maximum increase in PaCO₂ (17.17; p = 0.027) were recorded in group 2. There was a significant negative correlation between PaCO₂ and arterial blood pH in all the groups (r = –0.993; p < 0.01). The mean values of CBT decreases were statistically significant in all the groups: group 1 (p = 0.023), group 2 (p = 0.026), group 3 (p = 0.026), and “sham” group (p = 0.024). Conclusions The changes in PaCO₂ were directly proportional and the changes in pH contrarily proportional to the temperature of the insufflated CO₂. Significant differences in CBT decreases were found between the groups receiving heated gas and room temperature gas and the groups receiving heated gas and gas below room temperature.     

Pneumoperitoneum with carbon dioxide enhances liver metastases of cancer cells implanted into the portal vein in rabbits

Background: Little is known about the role of the CO₂ pneumoperitoneum on tumor cells that spread from the portal system into the liver during laparoscopic surgery for gastrointestinal malignancies. Therefore, we designed a study to investigate the effect of CO₂ pneumoperitoneum on cancer cells implanted in the portal vein in a rabbit model. Methods: Immediately after intraportal inoculation of 2.5 × 10⁵ cells of VX₂ cancer, the rabbits received either CO₂ pneumoperitoneum at a pressure of 10 mmHg for 30 min (pneumoperitoneum group, n= 14) or laparotomy alone for 30 min (laparotomy group, n= 14). Results: The number (p < 0.01) and area of cancer nodules (p= 0.045) on the liver surface on day 17 were greater in the pneumoperitoneum group than in the laparotomy group. The frequency of cancer nodules >3.0 mm in diameter was higher in the pneumoperitoneum group than in the laparotomy group (p < 0.001). Conclusions: Compared with laparotomy, CO₂ pneumoperitoneum enhanced the development of liver metastases in this experimental model. Received: 9 December 1998/Accepted: 3 April 1999     

Determination of cardiorespiratory function and the optimum anesthetic regimen during laparoscopic surgery in the rat model

Background: The rat is increasingly being used in laparoscopic research yet the hemodynamic and respiratory effects of CO₂ pneumoperitoneum have not been studied in this model. Methods: Five Lewis rats were anesthetized with inhaled isoflurane (1.4–2.0%) and a 50% O₂/50% N₂O mixture by mask (ISO). Another five rats were anesthetized with 1 ml/kg intraperitoneal sodium pentobarbital (PB) and given 100% O₂ by mask. Catheters were placed in the femoral artery and the right jugular vein and a thermistor probe was placed in the aortic arch. Heart rate (HR), blood pressure (MAP), cardiac index (CI), arterial pH, and PCO₂ were measured at baseline and following 10, 20, and 30 min of 2 mmHg CO₂ pneumoperitoneum. Results: CO₂ pneumoperitoneum had no effect on HR, MAP, CI, pH, or PCO₂ in either the ISO or PB anesthetic groups. Comparing the two anesthetic groups, PB demonstrated a significantly higher MAP at all time points, a significantly higher PCO₂ at baseline, and 10 min of pneumoperitoneum, a significantly lower pH at baseline, 10, and 30 minutes of pneumoperitoneum, and a significantly longer induction time (31 vs. 6 min). There was no difference in HR or CI between the two anesthetics. Conclusion: Low-pressure CO₂ pneumoperitoneum up to 30 min in the spontaneously breathing rat does not significantly affect HR, MAP, CI, pH, or PCO₂. Inhalational isoflurane/N₂O anesthesia produces less hypertension and respiratory acidosis than intraperitoneal pentobarbital during pneumoperitoneum in the rat.     

Hepatic and portal vein blood flow during carbon dioxide pneumoperitoneum for laparoscopic hepatectomy

Background: Laparoscopy under carbon dioxide (CO₂) pneumoperitoneum has many advantages. However, the risks of CO₂ pneumoperitoneum during laparoscopic hepatectomy (LH) have not been defined. Methods: The hemodynamics of the hepatic vein were examined during CO₂ pneumoperitoneum both pre- and posthepatectomy in eight pigs. Portal blood flow was measured with Doppler ultrasound during laparoscopic cholecystectomy in 10 human patients. Results: Experimentally, elevated intraabdominal pressure (IAP) with CO₂ insufflation produced significant increases in CO₂ partial pressure and echogenicity of the hepatic vein in the posthepatectomy group. Clinically, elevated IAP caused significant narrowing of the portal vein and significant decreases in portal blood velocity. The mean portal flow was significantly decreased with elevation of IAP >10 mmHg. Conclusions: LH with CO₂ pneumoperitoneum may lead to embolism caused by CO₂ bubbling through the hepatic vein. Elevated IAP may cause a decrease in hepatic blood flow and induce severe liver damage, especially in patients with poor liver function. Gasless laparoscopy using abdominal wall lifting should be employed in LH to avoid the risks of CO₂ embolism and liver damage. Received: 28 March 1997/Accepted: 12 September 1997