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     

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     

Duration of postlaparoscopic pneumoperitoneum

Background: Patients who present with abdominal pain after recent laparoscopic surgery present a diagnostic dilemma when pneumoperitoneum is present. Previous studies do not define the duration of postlaparoscopic pneumoperitoneum. In this study, we attempted to define the duration of laparoscopic pneumoperitoneum and to identify factors which affect resolution time. Methods: We followed 57 patients who underwent laparoscopic cholecystectomy (34), inguinal herniorraphy (20), or appendectomy (three). Serial abdominal films were taken until all residual gas was resolved. Results: Thirty patients resolved their pneumoperitoneum within 24 h; 16 patients resolved between 24 h and 3 days; nine patients resolved between 3 and 7 days; two patients resolved between 7 and 9 days. Mean resolution time for all patients was 2.6 ± 2.1 days. There was no apparent difference in resolution time between the three types of procedures; however, the sample size may be insufficient. Duration of the pneumoperitoneum did not correlate with gender, age, weight, initial volume of CO₂ used, length of time for the procedure, or postoperative complications. Sixteen patients had bile spillage during cholecystectomy which significantly reduced the duration of postoperative pneumoperitoneum (p < 0.008), resulting in a mean resolution time of 1.3 ± 0.9 days. While 14 patients reported postoperative shoulder pain, no correlation was found between the presence or duration of shoulder pain and the extent or duration of pneumoperitoneum. Conclusions: We conclude that the residual pneumoperitoneum following laparoscopic surgery resolves within 3 days in 81% of patients and within 7 days in 96% of patients. The resolution time was significantly less in patients sustaining intraoperative bile spillage during cholecystectomy. There was no correlation found between postoperative shoulder pain and the presence or duration of the pneumoperitoneum. Received: 22 March 1996/Accepted: 12 July 1996     

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     

Influence of CO2 pneumoperitoneum during laparoscopic surgery on cancer cell growth

Background: CO₂ pneumoperitoneum provides a new surgical environment to treat malignant disease. The purpose of this study was to investigate the influence of CO₂ pneumoperitoneum during laparoscopic surgery on cancer cell growth. Methods: WiDr human colon cancer cells were incubated for 3 h under the following two conditions: 100% CO₂ at 10 mmHg, and 95% air/5% CO₂ (control). Cell proliferation was assessed by the WST-1 assay and BrdU assay. Tumor growth was assessed by subcutaneous injection into 20 nude mice. Cellular damage was measured by lactate dehydrogenase (LDH) assay. Results: The number of WiDr cells under pneumoperitoneal conditions decreased in the first 24 h. However, no significant difference was observed in the proliferation rate and tumor growth of the viable cells. LDH release of the CO₂ pneumoperitoneal group was higher than that of the controls. Conclusions: Our data indicate that CO₂ pneumoperitoneum does not promote cancer cell proliferation but instead has a toxic effect on cancer cells. Received: 19 March 1999/Accepted: 15 June 1999     

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     

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     

Videoscopic surgery under local and regional anesthesia with helium abdominal insufflation

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

Postoperative drowsiness and emetic sequelae correlate to total amount of carbon dioxide used during laparoscopic cholecystectomy

Background: After laparoscopy with carbon dioxide (CO₂) insufflation early postoperative recovery is often complicated with drowsiness and postoperative nausea and vomiting (PONV). Methods: 25 ASA I − II patients undergoing elective laparoscopic cholecystectomy under standardized anaesthesia were studied in a randomized, prospective study. The conventional CO₂ pneumoperitoneum was compared with the mechanical abdominal wall lift (AWL) method with minimal CO₂ insufflation with special reference to postoperative recovery. Results: Postoperative drowsiness was of a significantly longer duration with the conventional method (p < 0.001) compared with the AWL technique. There was a positive correlation with the total amount of CO₂ used and the duration of drowsiness (r = 0.75, p < 0.01). PONV was seen significantly more often in patients with CO₂ insufflation of more than 121 (p < 0.05). Conclusions: Avoiding excessive CO₂ is beneficial for smoother and more uneventful recovery after laparoscopic cholecystectomy. Received: 11 January 1996/Accepted: 29 May 1996     

The adverse hemodynamic effects of anesthesia, head-up tilt, and carbon dioxide pneumoperitoneum during laparoscopic cholecystectomy

Background: The increased intra-abdominal pressure during pneumoperitoneum, together with the head-up tilt used in upper abdominal laparoscopies, would be expected to decrease venous return to the heart. The goal of our study was to determine whether laparoscopy impairs cardiac performance when preventive measures to improve venous return are taken, and to analyze the effects of positioning, anesthesia, and increased intra-abdominal pressure. Methods: Using invasive monitoring, hemodynamic changes were investigated in 15 ASA class I or II patients under isoflurane–fentanyl anesthesia during laparoscopic cholecystectomy. Before laparoscopy, the patients received an intravenous (IV) infusion of colloid solution if cardiac filling pressures were low, and their legs were wrapped from toes to groin with elastic bandages. Measurements were taken while the patients were awake in the supine (baseline) and head-up tilt (15–20°) positions, and after the induction of anesthesia in the same positions. Measurements were repeated at regular intervals during laparoscopy (intra-abdominal pressure at 13–16 mmHg), after deflation of the gas, and in the recovery room. Results: With the passive head-up tilt in awake and anesthetized patients, the cardiac index (CI), stroke index (SI), central venous pressure (CVP), and pulmonary capillary wedge pressure (PCWP) decreased, and systemic vascular resistance increased. With the patient under anesthesia, SI decreased, but CI did not change significantly as a result of the compensatory increase in heart rate. Carbon dioxide (CO₂) insufflation at the start of laparoscopy produced increases in CVP and PCWP as well as mean systemic and mean pulmonary arterial pressures without changes in CI or SI. Toward the end of the laparoscopy, CI decreased by 15%. The hemodynamic values returned to nearly prelaparoscopic levels after deflation of the gas, and CI was elevated during the recovery period, whereas systemic vascular resistance was decreased in comparison with the baseline. Conclusions: By correcting relative dehydration and preventing the pooling of blood, CI decreased less than 20% during pneumoperitoneum as compared with the baseline awake level. The head-up positioning accounts for many of the adverse effects in hemodynamics during laparoscopic cholecystectomy. Received: 6 November 1998/Accepted: 8 July 1999     

Effect of CO2 insufflation on bacteremia and bacterial translocation in an animal model of peritonitis

Background: The widespread adoption of the laparoscopic approach has created some concern over the potential for increased risk of bacteremia and sepsis due to increased intraabdominal pressure in patients with intraabdominal infection and peritonitis. This study examines the effect of the CO₂ pneumoperitoneum on bacteremia and bacterial translocation. Methods: New Zealand white rabbits were assigned into three groups of 10 animals. In group 1, 100 ml of sterile saline was infused into the peritoneal cavity under 10 mmHg CO₂ insufflation for 1 h. Group 2 received 100 ml of saline containing 10⁹ CFU/ml (colony-forming units) E. coli strain 0163 and 10 mmHg CO₂ insufflation for 1 h. Group 3 received an identical bacterial inoculum, followed by a 10-cm midline laparotomy. Blood samples were taken for culture by cardiac puncture at various intervals during the experiment. At 6 h after being subjected to the experimental procedures, the rabbits were killed and their organs were cultured quantitatively for translocating bacteria. Results: In group 1, neither blood nor organ cultures were positive, whereas in group 2 all blood cultures became positive in 1 h, and intraperitoneally infused bacteria translocated to the lung and kidney in all rabbits. In group 3, blood cultures became positive in 1 h, all but two of the rabbits had translocated bacteria in their lungs, and kidney samples from two of the rabbits were culture-positive. Conclusions: Our results indicate that both CO₂ pneumoperitoneum and laparotomy increase the incidence of bacterial translocation from the peritoneal cavity into the bloodstream. Thus, the risk of translocation to extraperitoneal organs such as lung and kidney is increased significantly by laparoscopy. Therefore, laparoscopic surgery should be avoided or used cautiously in the setting of acute peritonitis.     

Randomized comparison between low-pressure laparoscopic cholecystectomy and gasless laparoscopic cholecystectomy

Background: Laparoscopic cholecystectomy using low-pressure pneumoperitoneum (8 mmHg) minimizes adverse hemodynamic effects, reduces postoperative pain, and accelerates recovery. Similar claims are made for gasless laparoscopy using abdominal wall lifting. The aim of this study was to compare gasless laparoscopic cholecystectomy to low-pressure cholecystectomy with respect to postoperative pain and recovery. Methods: Thirty-six patients were randomized to low-pressure or gasless laparoscopic cholecystectomy using a subcutaneous lifting system (Laparotenser). Results: The characteristics of the patients were similar in the two groups. The procedure was completed in all patients in the low-pressure group, but two patients in the gasless group were converted to pneumoperitoneum. There were no significant differences in postoperative pain and analgesic consumption, but patients in the gasless group developed shoulder pain more frequently (50% vs 11%, p < 0.05). Gasless operation took longer to perform (95 vs 72.5 min, p= 0.01). Conclusions: Gasless and low-pressure laparoscopic cholecystectomy were similar with respect to postoperative pain and recovery. The gasless technique provided inferior exposure and the operation took longer, but the technique may still have value in high-risk patients with cardiorespiratory disease. Received: 10 August 1998/Accepted: 12 February 1999     

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     

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     

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     

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     

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     

Transesophageal echocardiographic assessment of hemodynamic function during laparoscopic cholecystectomy in healthy patients

Background: This study aimed by means of transesophageal echocardiography, to evaluate hemodynamic changes induced by pneumoperitoneum in patients with normal cardiac performance. Methods: In this study, 11 ASA I–II patients (mean age, 39 years) with normal cardiac performance undergoing laparoscopic cholecystectomy were evaluated. A 5-MHz transesophageal biplane phased-array transducer connected to an echocardiographer was inserted after induction of anesthesia. Data were collected at three different times: before insufflation (T1), 10 min after insufflation (T2), and 5 min after desufflation (T3). At these same times, heart rate, systolic blood pressure, diastolic blood pressure, end-tidal carbon dioxide (CO₂), and peak airway pressure were recorded. Statistical analysis was performed using one-way and two-way analysis of variance (ANOVA). A p value less than 0.05 was considered significant. Results: End-systolic and end-diastolic diameters of the left ventricle, contractility, and performance parameters did not change significantly. Conversely, at insufflation, color Doppler area of the mitral backflow increased significantly (p < 0.05) when already present or showed up abruptly (T1: 0.22 ± 0.28 cm²; T2: 1.28 ± 1.02 cm²; T3: 0.49 ± 0.53 cm²). Conclusions: Such an event is not interpreted as a mitral insufficiency. It is possibly the result of a ``contrast effect' caused by the absorption of CO₂ microbubbles in the blood. Received: 12 April 1998/Accepted: 23 June 1999