Intraperitoneal tumor growth is influenced by pressure of carbon dioxide pneumoperitoneum

Background: Several studies have indicated that the carbon dioxide (CO₂) pneumoperitoneum during laparoscopy plays a role in the pathogenesis of port-site metastases. An experimental animal study was performed to investigate the impact of various pneumoperitoneum pressures on peritoneal tumor growth. Methods: In this study, 36 male WAG rats were randomized into three groups; two groups with different pneumoperitoneum pressures (16 mmHg and 4 mmHg) and one group of gasless controls. After a pneumoperitoneum of 0.5 × 10⁶ ml was established, 531 tumor cells were injected intra-abdominally and the pneumoperitoneum was maintained for 60 min. Peritoneal tumor growth was assessed on day 11 at autopsy. Results: Peritoneal tumor growth in the 16-mmHg group was significantly greater than in the 4-mmHg group (p= 0.039) and the gasless group (p= 0.004). Conclusions: High-pressure CO₂ pneumoperitoneum stimulates intra-abdominal tumor growth. The use of low insufflation pressures in laparoscopic cancer surgery should be considered. Received: 1 December 1998/Accepted: 10 July 1999/Online publication: 9 August 2000     

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     

A serum-soluble factor(s) stimulates tumor growth following laparotomy in a murine modelrid=""id=""Presented at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), San Antonio, TX, 26 March 1999

Background: Our laboratory and others have previously demonstrated that tumors grow larger and are more easily established following laparotomy than after CO₂ pneumoperitoneum. The etiology of increased tumor growth after surgery is unknown. We hypothesized that, following laparotomy, a serum soluble factor(s) is generated that causes tumors to proliferate more rapidly. The purpose of the current study was to determine if in vitro tumor cells proliferate faster when incubated with serum from laparotomized mice than cells incubated with sera from mice who have undergone CO₂ pneumoperitoneum or anesthesia alone. Methods: In the first experiment, female Balb/C mice (n= 84) were randomly divided into the following three groups: (a) control (AC), (b) CO₂ insufflation (INS), and (c) laparotomy (OPEN). The AC mice underwent no procedure. The INS group underwent CO₂ pneumoperitoneum at 4–6 mmHg for 20 min. The OPEN group had a midline incision from xiphoid to pubis. The serum of seven mice from each group were collected on postoperative days (POD) 1, 2, 4, and 7 via a cardiac puncture. The sera at each time point for each group were pooled. Twenty thousand C-26 colon cancer cells were incubated separately in growth media containing 10% mouse serum from each group (seven determinations/group) at each time point. In the second experiment, female Balb/C (n= 30) mice were divided into AC and OPEN groups. On POD4, sera were collected and pooled. Three separate studies were performed for the second experiment. In the first study, tumor cells were incubated with 10% AC sera or varying concentrations of OPEN mice sera (4–10%). In the second study, aliquots of sera from the OPEN group mice were then heated at 100°C for 1 or 5 min. Tumors were then incubated separately in media with 10% AC, OPEN, or heated OPEN group sera. In the third study, aliquots of sera from the OPEN group mice were dialyzed against PBS through a 3.5-kD or an 8-kD dialysis membrane tubing for 24 h. Tumors were then incubated separately in media with 10% AC, OPEN, or dialyzed OPEN group sera. For both experiments, tumor proliferation was determined and compared between groups after 72 h of incubation. Results: Tumor cells incubated with POD2 and POD4 sera from OPEN group mice proliferated twice as fast as those incubated with sera from either AC or INS group mice. The difference in proliferation was maximal on POD4 and started to decline by POD7. Proliferative activity from the OPEN group sera decreased significantly when heated for 1 min and was completely ablated after 5 min of heating. Proliferative activity from the OPEN group sera was completely ablated after dialysis. Conclusions: We conclude that there is a serum-soluble factor(s) present postoperatively that stimulates tumors to grow significantly faster after laparotomy. The mitogenic effect of laparotomized mice sera is dilutable. It is uncertain whether the factor is heat labile, since heating most likely destroys other necessary proteins in the sera. The size of the factor is undeterminable using the dialysis method. Further efforts to identify these factors are currently underway. Received: 8 February 1999/Accepted: 23 June 1999/Online publication: 24 March 2000     

Oxidative stress in lung tissue induced by CO2 pneumoperitoneum in the rat

Background: Clinical trials have found that the pneumoperitoneum has potentially hazardous side effects. The biochemical basis of organ injury induced by pneumoperitoneum is, however, not well defined. Since oxidative stress is believed to play an important role in many pathological conditions, we set out to examine oxidative stress markers in the lung, liver, kidney, and pancreas by using a rat model of laparoscopy with CO₂ pneumoperitoneum and comparing it to a group with gasless laparoscopy. Methods: Malondialdehyde (for lipid peroxidation), protein-bound carbonyls (for protein oxidation), reduced and oxidized glutathione, and the neutrophil marker myeloperoxidase were evaluated in tissue homogenates at 2 h, 6 h, and 18 h after laparoscopy. Immunoblotting was used to analyze the modification of lung proteins by 4-hydroxynonenal at 6 h. Results: Significant lipid peroxidation was found selectively in lungs at 2 h and 6 h after CO₂ pneumoperitoneum. This was accompanied by a loss of glutathione but only minor protein oxidation. Further, lung proteins were clearly modified by the aldehydic product of lipid peroxidation 4-hydroxynonenal. Myeloperoxidase in lungs increased continuously up to 18 h in both experimental groups, but there were higher levels in the group with pneumoperitoneum. Conclusion: Oxidative stress is likely to contribute to the impairment of pulmonary function after laparoscopic operations using a CO₂ pneumoperitoneum. Received: 22 November 1999/Accepted: 22 March 2000/Online publication: 10 July 2000     

The effect of carbon dioxide pneumoperitoneum on free radicals

Background: Carbon dioxide is usually preferred as the insufflating agent for laparoscopic surgery because it is readily available, noncombustible, and chemically stable. It is still questionable, however, if CO₂ pneumoperitoneum has any effect on free radicals and lipid peroxidation. The purpose of this study was to investigate the possible effects of CO₂ pneumoperitoneum on free radicals and lipid peroxidation in the erythrocytes of rats. Methods: Fifty male Sprague-Dawley rats were divided into five equal groups: controls, a sham-operation group, and three groups of 5, 10, or 15 mmHg pneumoperitoneum with CO₂. At the end of the procedure, blood was collected and the erythrocytes were separated from the plasma. The resultant supernatant fractions of erythrocytes were assayed for superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). Results: SOD activities of the 5 and 10 mmHg pneumoperitoneum groups were significantly lower than those of the sham operation group. SOD activity was greater in the 15 mmHg pneumoperitoneum group than in any of the other groups, and this activity was significantly different from that seen in the 5 and 10 mmHg pneumoperitoneum groups (p < 0.05). No significant changes were observed in the CAT activities of the study groups (p > 0.05). MDA level was increased in the 5 mmHg pneumoperitoneum group; this result was statistically different from the control and 15 mmHg pneumoperitoneum groups (p < 0.05). No significant differences were found in the CAT activities for the study groups. On the other hand, the SOD activities of the 5 and 10 mmHg pneumoperitoneum groups were significantly lower than those of the sham and the 15 mmHg pneumoperitoneum group (p < 0.05 for all comparisons). Conclusions: These results indicate that CO₂ pneumoperitoneum applied with 5–10 mmHg pressure increases the formation of free oxygen radicals by inhibiting SOD activity and that the accumulation of free radicals elevates the level of MDA, a metabolite of lipid peroxidation. The effect of CO₂ pneumoperitoneum on free radicals and lipid peroxidation is pressure-dependent in rats. The mechanism underlying this pressure dependency is still under investigation. Received: 16 December 1999/Accepted: 14 February 2000/Online publication: 10 May 2000     

Characteristic alterations of the peritoneum after carbon dioxide pneumoperitoneum

Objective: Any route of entry into the abdomen contributes to alterations of the intraperitoneal organs with different clinical consequences. Characteristic alterations of the peritoneum after CO₂ pneumoperitoneum used in laparoscopic surgery is examined. Methods: A CO₂ pneumoperitoneum with an intraperitoneal pressure of 6 mmHg was applied for 30 min in 32 nude mice. In the course of 4 days, the animals were killed and the peritoneal surface of the abdominal wall was studied by means of scanning electron microscopy. Results: Already 2 h after release of the pneumoperitoneum, mesothelial cells were bulging up. The intercellular clefts thereby increased in size, and the underlying basal lamina became visible. This reaction peaked after 12 h. Subsequently, peritoneal macrophages and lymphocytes filled all gaps, thereby recovering the basal lamina. Conclusion: The morphologic integrity of the peritoneum is temporarily disturbed by a CO₂ pneumoperitoneum. Received: 9 March 1998/Accepted: 24 July 1998     

Influence of nitrous oxide anesthesia on venous gas embolism with carbon dioxide and helium during pneumoperitoneum

Background: Gas embolism is a potential hazard during laparoscopic procedures. The aim of this study was to evaluate the effects of nitrous oxide (N₂O) inhalation in the case of gas embolism with carbon dioxide (CO₂) and helium during pneumoperitoneum. Methods: For this study, 20 anesthetized pigs were ventilated with N₂O (67% inspired) in O₂ (n= 10) or with halothane (0.7–1.5 inspired) in O₂ (n= 10). In each group, CO₂ (n= 5) or helium (n= 5) pneumoperitoneum was established and gas embolism induced at different rates (CO₂ at 0.5, 1, or 2 ml/kg/min; helium at 0.025, 0.05, or 0.1 ml/kg/min) through the left femoral vein a maximum of 10 min while all hemodynamic parameters were continuously monitored. Results: In the CO₂ group without N₂O, all the animals tolerated rates of 0.5 and 1 ml/kg/min over the 10 min, whereas only 3 of 4 animals in the CO₂ group with N₂O tolerated a rate of 0.5 ml/kg/min, and 2 of 4 animals a rate of 1 ml/kg/min. In the helium group without N₂O, all the animals tolerated gas embolism at all rates, whereas in the helium group with N₂O, 4 of 5 animals needed to be resuscitated at a rate of 0.1 ml/kg/min and one death occurred. Conclusions: Inhalation of N₂O worsens the negative cardiovascular effects of venous CO₂ or helium gas emboli and increases the risk of emboli-induced death when CO₂ or helium are used to establish pneumoperitoneum. The volume of venous venous helium gas emboli causing such effects is substantially smaller than that for venous CO₂ gas emboli. Received: 20 September 1999/Accepted: 1 October 2000/Online publication: 4 August 2000     

Effect of pressure and gas type on intraabdominal, subcutaneous, and blood pH in laparoscopy

Background: According to the literature, the number of port-site metastases in laparoscopic surgery varies considerably depending on the type of gas used for the pneumoperitoneum. In order to investigate this observation we studied the changes in blood, subcutaneous, and intra-abdominal pH during laparoscopy with helium, CO₂ and room air in a rat model. In addition, we looked at the influence of intra-abdominal pressure and duration of pneumoperitoneum on the pH during the laparoscopy. Methods: pH was measured by tonometry, intra-abdominally and subcutaneously. A pH electrode was additionally placed into the subcutaneous tissue and the results compared to those measured by tonometry. Blood samples were taken from a catheter in the carotid artery. The intra-abdominal pressure was 0, 3, 6, 9 mmHg for 30 min in each case. We investigated the effect of pneumoperitoneum with CO₂, helium and air in randomized groups of 5 rats. In an additional series the pressure was held constant at 3 mmHg and the pH was measured every 30 min. Results: Due to the different absorption capacity of the peritoneum, laparoscopy with CO₂ decreases the subcutaneous pH from 7.35 to 6.81. Blood pH is reduced from 7.37 to 7.17 and the intra-abdominal pH from 7.35 to 6.24. Other, less absorbable gases induce smaller changes of blood and subcutaneous pH (only 10% of CO₂). In a variance analysis the p value is less than 0.001. The influence of duration of laparoscopy (30 min vs 90 min) on the subcutaneous pH is less compared to the influence of intra-abdominal pressure (0, 3, 6, 9 mmHg). Conclusions: Depending on the type of gas (CO₂, air, helium) used for laparoscopy blood, subcutaneous and intra-abdominal pH are influenced differently. Because lower pH is known to impair local defense mechanisms, these results may be one explanation for the higher incidence of port-site metastasis in laparoscopy with CO₂ than with other gases, as reported in the literature. Received: 11 June 1998/Accepted: 12 February 1999     

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     

Port-site metastases

Background: Port-site metastases after laparoscopic procedures in patients with digestive malignancies have evoked concern. The pathogenesis of port-site metastases remains unclear. Two experiments in rats were performed to determine the impact of both tissue trauma and leakage of CO₂ along trocars (chimney effect) in the development of port-site metastases. Methods: Experiment I: Ten WAG rats had four 5-mm incisions in all abdominal quadrants. The incisions on the right side were crushed to induce tissue trauma. After inserting 5-mm trocars in all incisions, a pneumoperitoneum was created, and CC-531 tumor cells were injected intraperitoneally. CO₂ was insufflated for 20 min. Experiment II: Ten WAG rats had 5-mm incisions in the left and right abdominal upper quadrant. A 5-mm trocar was inserted in the incision in the left upper quadrant, and a 2-mm trocar was inserted in the incision in the right upper quadrant. After insufflating the abdomen, CC-531 tumor cells were injected intraperitoneally. Total leakage of CO₂ along the trocar in the right quadrant was 10 liters. After 4 weeks, in both experiments, the tumor deposits at the trocar sites were assessed. Statistical analysis was performed by the Wilcoxon matched-pairs test. Results: Experiment I: The median weight of tumor deposits at the trocar sites without induced tissue trauma was 22 mg. At the traumatic port sites, median weight of tumor deposits was 316 mg (p= 0.007). Experiment II: The median weight of tumor deposits at the leaking trocar sites was 478 mg and at the control sites 153 mg (p= 0.009). Conclusion: Tissue trauma at trocar sites and leakage of CO₂ along a trocar appear to promote implantation and growth of tumor cells at port sites. Received: 15 May 1997/Accepted: 3 March 1998     

Alterations in hemodynamics and left ventricular contractility during carbon dioxide pneumoperitoneum

Background: Carbon dioxide (CO₂) pneumoperitoneum has been shown to adversely affect hemodynamics in patients. This study specifically examines the potential contribution of altered left ventricular contractility (LVC) to hemodynamic changes observed during CO₂ pneumoperitoneum. Methods: In a canine model, LV volumes, LV pressure, and intrathoracic and central venous pressures were recorded both at basal intra-abdominal pressure (IAP) and after CO₂ insufflation to produce IAPs of 5–25 mmHg. Results: At IAPs greater than 15 mmHg, cardiac output and LV end-diastolic volume decreased. Mean arterial pressure and heart rate were unchanged. LVC, quantified using the linear Frank-Starling relationship, was not affected by increases in IAP. Conclusions: This study is the first to quantify LVC during CO₂ pneumoperitoneum and demonstrates no changes in contractility over IAPs from 5 to 25 mmHg. In the dog model, any hemodynamic alterations induced by CO₂ pneumoperitoneum are secondary to altered LV preload and not alterations in contractility or LV afterload. Received: 8 March 1996/Accepted: 23 April 1996     

Feasibility of therapeutic pneumoperitoneum in a large animal model using a microvaporisator

Background: Multimodal therapy is used increasingly in advanced gastrointestinal tumors. Potential benefits of using an intraoperative adjuvant therapy during laparoscopy for cancer have been documented in animal studies. The aim of this study was to develop a device that could deliver such an intraoperative drug therapy. Methods: We developed a micropump suitable for minimally invasive surgery procedures that allowed microdroplets of therapeutic substance to be distributed into the pneumoperitoneum (CO₂), creating a ``therapeutic pneumoperitoneum.' A closed-loop control system regulates drug delivery according to the gas flow. In vitro, the micropump is able to aerosolize various aqueous and ethanol solutions, including cytostatic and bacteriostatic drugs and adhesion-modulating agents. The size of the microdroplets has been optimized to prevent visual artifacts. Results: The micropump was tested in an animal model (pig). The system was inserted into a 5-mm trocar. After insufflation of a 12-mm CO₂ pneumoperitoneum, laparoscopic sigmoid colon resections could be performed with no special difficulties. No fog developed, and no system-related complication was observed. At autopsy, the active principle was distributed to all exposed peritoneal surfaces. Conclusions: As opposed to conventional peritoneal washing, therapeutic pneumoperitoneum reaches the entire peritoneal surface, allowing an optimal drug distribution. Drug diffusion into the tissues is enhanced by the intraperitoneal pressure. Precise determination of the instantaneous and total drug quantity is possible. Therefore, this drug delivery system has several advantages over conventional irrigation. Its potential domains of application are locoregional cancer therapy, prevention of port-site recurrences, immunomodulation, analgesia, peritonitis, and prevention of postoperative adhesions. Received: 27 May 1998/Accepted: 5 January 1999     

Effects of pneumoperitoneum on cardiac autonomic nervous activity evaluated by heart rate variability analysis during sevoflurane, isoflurane, or propofol anesthesia

Background: The effects of pneumoperitoneum on the activity of the cardiac autonomic nervous system have not been completely understood. Methods: In this study, 45 unpremedicated adult patients who underwent laparoscopic cholecystectomy were anesthetized with either 3.5% sevoflurane, 2% isoflurane, or 8 mg/kg/h propofol (15 patients in each group). The status of cardiac autonomic nervous activity was evaluated by heart rate variability analysis three times: once when the patient was awake, once after induction of general anesthesia, and once after insufflation for pneumoperitoneum. Intra-abdominal pressure was maintained automatically at 10 mmHg by a carbon dioxide (CO₂) insufflator. For each measurement, electrocardiogram was recorded for 256 s and played back offline to detect R-R intervals. Power spectral analysis of heart rate variability was applied, and the low-frequency (LF, 0.04–0.15 Hz) and high-frequency (HF, 0.15–0.40 Hz) bands of the spectral density of the heart rate variability were obtained from a power spectra of R-R intervals using the fast-Fourier transform algorithm. The HF/LF ratio also was analyzed. Results: Measurements of heart rate variability in the three groups showed similar change. Although the power of HF, which represents parasympathetic nervous activity, did not change, the power of LF, which represents both sympathetic and parasympathetic nervous activity, decreased during the anesthetized stage and increased during the insufflated stage. The HF/LF ratio, which represents the balance of parasympathetic and sympathetic activity, increased after induction of general anesthesia, and decreased after insufflation. Conclusions: Our results suggest that pneumoperitoneum increases sympathetic cardiac activity. The choice of general anesthetic did not seem to have a major influence on the change in the cardiac autonomic nervous system after induction of pneumoperitoneum for laparoscopic cholecystectomy. Received: 22 January 1999/Accepted: 22 March 1999     

Intraperitoneal immunity and pneumoperitoneum

Background: Carbon dioxide (CO₂) pneumoperitoneum has been implicated as a possible factor in depressed intraperitoneal immunity. Using in vitro functional assays, CO₂ has been shown to decrease the function of peritoneal macrophages harvested from insufflated mice. However, an effective in vivo assessment is lacking. Listeria monocytogenes (LM), an intracellular pathogen, has served as a well-established in vivo model to study cell-mediated immune responses in mice. This study examines the immune competence of mice based on their ability to clear intraperitoneally administered LM following CO₂ vs helium (He) insufflation. Methods: Eighty-five mice (C57Bl/6, males, 4–6 weeks old) were divided between the following four treatment groups: CO₂ insufflation, He insufflation, abdominal laparotomy (Lap), and control (anesthesia only). Immediately postoperatively, each group was inoculated percutaneously and intraperitoneally with a sublethal dose (.015 × 10⁶ org) of virulent LM (EGD strain). Half of the animals were killed on postoperative day 3 and half on day 5. Spleens and livers (sites of bacterial predilection) were harvested, homogenized, and plated on TSB agar. The amount of bacteria (1 × 10⁶ LM/spleen and liver) from each group was then compared. Statistical significance was set at p≤ 0.05. Results: Control animals had nominal bacteria on day 3 (0.016 × 10⁶ LM/spleen and liver), and the bacterial burden remained low at day 5 (0.038 × 10⁶ LM/spleen and liver) postchallenge. On day 3, the bacterial burden was significantly higher in the CO₂ group (5.46 × 10⁶ LM/spleen and liver) as compared to He (0.093 × 10⁶ LM/spleen and liver) and controls. The Lap group (3.44 × 10⁶ LM/spleen and liver) had significantly more bacteria than the controls. There were no significant differences between any of the groups on day 5. Conclusions: In this animal model, CO₂ pneumoperitoneum impaired cell-mediated intraperitoneal immunity significantly more than He pneumoperitoneum and controls on day 3. Also on day 3, laparotomy caused impairment of intraperitoneal immunity when compared to controls. Finally, intraperitoneal immunosuppression resolved by day 5. Received: 22 July 1998/Accepted: 3 March 1999     

The influence of different insufflation pressures during carbon dioxide pneumoperitoneum on the development of pulmonary metastasis in a mouse model

Background: The effects of different insufflation pressures on the development of pulmonary metastasis was investigated in a mouse laparoscopy model. Methods: BALB/C mice intravenously inoculated with colon 26 cells were randomized to one of five treatment groups (10 mice per group): pneumoperitoneum at different pressures of 5, 10 or 15 mmHg; full laparotomy for 60 min; or anesthesia control. Cancer nodules on the lung surface 19 days postoperatively were compared between groups. Results: (a) As compared with the control group, pneumoperitoneum at 10 and 15 mmHg and laparotomy enhanced the growth of pulmonary metastases (p < 0.01). (b) The growth of metastases also was greater in laparotomy group mice than in mice undergoing pneumoperitoneum at 5 and 10 mmHg (p < 0.05). Conclusions: These results suggest that the effects of different insufflation pressures on the growth of pulmonary metastases are not identical, and that pneumoperitoneum with high pressure may promote pulmonary metastases similar to those with laparotomy. Received: 4 November 1999/Accepted: 20 December 1999/Online publication: 25 April 2000     

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     

Acid–base balance alterations in laparoscopic cholecystectomy

Background: The purpose of this study is to determine alterations of acid–base balance originated by pneumoperitoneum with CO₂. Influence of other factors such as anesthetic technique, duration of procedure, and volume of CO₂ insufflated has also been analyzed. Methods: Some 132 patients were divided in three groups according to anesthetic technique used. Arterial blood gases were determined before pneumoperitoneum, at 20 min after it, and every 30 min, until procedure's end, and in postoperative period up to a total of four samples. Results: Pneumoperitoneum originated a fall of pH (p < 0.001), ion bicarbonate (p < 0.001), and base excess (p < 0.001) and an elevation of PaCO₂ (p < 0.001). No correlation was found between these changes and duration of pneumoperitoneum or amount of CO₂ insufflated. Changes were fundamentally of a metabolic type. There were no statistically significant differences among anesthetic techniques. Conclusions: In conclusion, pneumoperitoneum with CO₂ originates alterations of the acid–base balance, mostly of a metabolic type. This could mean that besides CO₂ absorption, there is a tissular hypoperfusion due to the increase of abdominal pressure. Received: 25 January 1996/Accepted: 29 May 1996     

Reliable noninvasive parameters for early detection of cardiopulmonary compromise induced by carbon dioxide thoracoretroperitoneum in minimally invasive thoracolumboendoscopic spine surgery

Background: Using a novel endoscopic retroperitoneal approach for thoracolumbar anterior spine fusion, we examined the cardiopulmonary effects of the inevitably associated carbon dioxide (CO₂) thoracoretroperitoneum and evaluated noninvasive parameters, which may provide early and adequate recognition of cardiopulmonary dysfunction. Methods: Under balanced anesthesia and paralysis, six pigs subjected to endoscopic CO₂ thoracoretroperitoneal spine fusion underwent extensive pulmonary and hemodynamic online monitoring throughout the operative procedure. Open thoracophrenolumbotomy in six pigs served as a control procedure. Results: In contrast to unchanged cardiopulmonary parameters during open thoracolumbar spine surgery, CO₂ thoracoretroperitoneum caused significant hypercapnia, hypoxia, and acidemia with concomitant tachycardia, pulmonary hypertension, and systemic hypotension. Ventilatory adjustment, CO₂ evacuation, or both promptly reversed the cardiopulmonary effects. Noninvasively assessed end-tidal CO₂, peak respiratory pressure, and heart rate were early clues for detecting the tension pneumothorax-like cardiopulmonary dysfunction, as indicated by a significant correlation with the invasively assessed pulmonary hemodynamic parameters and arterial blood gases. Conclusions: During endoscopic thoracolumbar spine fusion, CO₂ thoracoretroperitoneum induces cardiopulmonary dysfunction, which, however, can be detected reliably by changes in end-tidal CO₂, peak respiratory pressure, and heart rate, and which can be corrected immediately by appropriate ventilatory adjustments. Therefore, endoscopic CO₂ thoracoretroperitoneal spine fusion might not necessarily require extraordinarily extensive and invasive monitoring of systemic and pulmonary hemodynamics, but ventilatory adjustment and intrathoracic pressure evacuation should be readily available to reexpand the lung, and to facilitate rapid normalization of hemodynamic conditions. Received: 1 April 1999/Accepted: 10 August 1999/Online publication: 4 August 2000     

Portal venous flow during CO2 pneumoperitoneum in the rat

Backround: CO₂ gas insufflation is routinely used to extend the abdominal wall. The resulting pneumoperitoneum has a number of local and systemic effects on the organism. Portal blood flow, which plays an important role in hepatic function and cell-conveyed immune response, is one of the affected parameters. Methods: An established animal model (rat) of laparoscopic surgery was modified by implanting a perivascular flow probe. Hemodynamics in the portal vein were then measured during increasing intraabdominal pressure generated by carbon dioxide insufflation. Results: Using this technique, an adequate flowmetry of the portal vein was achieved in all animals. The creation of a CO₂ pneumoperitoneum with increasing intraabdominal pressure led to a linear decrease in portal venous flow. Conclusions: Elevated intraabdominal pressure caused by carbon dioxide insufflation may compromise hepatic function and cell-conveyed immune response during laparoscopic surgery. Received: 28 January 1998/Accepted: 22 June 1998     

Effect of temperature of insufflated CO2 during and after prolonged laparoscopic surgery

Background: Pneumoperitoneum with room temperature carbon dioxide (CO₂) has been shown to decrease core temperature and urine output. Methods: The effect of 37°C (warm) and room temperature (cool) CO₂ pneumoperitoneum on core temperature, urine output, and central hemodynamics was compared in 26 randomized patients undergoing prolonged laparoscopic surgery (>90 min). Results: The core temperature (p < 0.05) and cardiac index (p < 0.05) were significantly higher after warm than after cool pneumoperitoneum. Urine output was significantly higher during warm (2.3 ± 1.6 ml/kg/h) than during cool (0.9 ± 0.7 ml/kg/h) insufflation (p < 0.05). Two of 13 patients with warm and 11 of 13 patients with cool pneumoperitoneum needed mannitol to maintain adequate diuresis (p < 0.05). Conclusions: Warm insufflation probably causes a local vasodilation in the kidneys and may be beneficial to patients with borderline renal function. Received: 23 June 1997/Accepted: 16 November 1997