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     

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 carbon dioxide pneumoperitoneum on bacteremia and severity of peritonitis in an experimental model

Background: Laparoscopy is increasingly used in conditions complicated by peritonitis. A theoretical concern is that carbon dioxide pneumoperitoneum may increase bacteremia. Method: In 60 rats peritonitis was induced by cecostomy. Animals were randomly allocated to pneumoperitoneum (PP) and control groups. Blood cultures and intraabdominal swabs were assessed. A peritonitis severity score (PSS) was computed based on histology from peritoneal biopsy. Results: One hour after cecostomy neither in abdominal swabs nor in blood samples bacteria were reproduced in PP and control groups. Three hours after cecostomy the frequency of positive blood cultures was 80% and 20% in PP and control groups, respectively (p < 0.0001). Six hours after cecostomy the frequency of positive blood cultures was 100% in each group (p > 0.05). One hour after cecostomy the mean peritoneal severity score was significantly higher in the PP group than in the control group, but there was not any significant difference between groups 3 and 6 h after cecostomy. The mean peritoneal severity scores were found to be significantly increased with time when the PP groups compared with each other. Conclusion: In rats, pneumoperitoneum can't cause a more severe peritonitis but it does induce an increase in the rate of bacteremia within the early 6-h period of peritonitis. Received: 14 April 1997/Received: 18 September 1997     

Influence of acute hemorrhage and pneumoperitoneum on hemodynamic and respiratory parameters

Background: We examined the questions of whether resuscitated (compensated) acute hemorrhage enhances the negative effects of carbopneumoperitoneum on hemodynamic and respiratory parameters and whether pneumoperitoneum with helium has any advantages under these circumstances. Our investigation focused on the influence of acute hemorrhage with different gases on the cardiovascular and respiratory system as well as on hepatic and renal blood flow in a porcine model. Methods: Cardiac and hemodynamic function were monitored via implantation of catheters in pulmonary artery, femoral vein, and artery. Renal and hepatic blood flow were recorded using a transonic volume flow meter placed at the renal and hepatic artery and portal vein. Twelve animals were randomly assigned to one insufflation gas (carbon dioxide [CO₂] or helium [He]). Following baseline recordings, acute hemorrhage (20 ml/kg) was induced by continuous bleeding over 30 min. Animals then received a colloidal solution (20 ml/kg 6% hydroxyethylstarch solution) over 30 min. Pneumoperitoneum of 12 mmHg was established, and all parameters were measured after 30 min of adaptation. The major endpoints of the study were cardiac output (CO), arterial pressure (MAP), systemic vascular resistance (SVR), and central venous pressure (CVP), as well as blood flow in hepatic and renal artery and portal vein. Results: While CO and hemodynamic parameter as well as hepatic and renal blood flow were markedly reduced after hemorrhage, they returned nearly to their previous levels after resuscitation. Pneumoperitoneum with 12 mmHg did not further depress the cardiovascular system or reduce hepatic and renal blood flow. Pneumoperitoneum did not alter hepatic or renal blood flow. Pneumoperitoneum with helium did not substantially change the reaction of the cardiovascular system after resuscitated hemorrhage. Conclusions: If hemorrhage is compensated by proper resuscitation and hypovolemia is avoided, laparoscopic surgery with pneumoperitoneum of 12 mmHg appears to be not harmful. Using helium as the insufflating gas had no clear advantage over the carbon dioxide model. Received: 30 July 1997/Accepted: 24 October 1997     

The effects of pneumoperitoneum on gastric blood flow and traditional hemodynamic measurements

Background: The purpose of this study was to investigate the effects of increasing intraabdominal pressure (IP) on gastric blood flow, as measured by gastric tonometry and traditional hemodynamic measurements. Methods: Nine swine were anesthetized, intubated, and ventilated. Arterial and pulmonary artery catheters were placed by cutdown, a trocar was placed in the abdomen, and a gastric tonometer was placed in the stomach. Serial measurements of arterial and mixed venous blood gases, cardiac output, wedge pressure, lactic acid, and gastric intramucosal pH (pH_i) were collected at intraperitoneal pressures of 0, 8, 10, 12, 14, 16, and 18 mm Hg after 30 min equilibration. Statistical analysis included Pearson correlation and Student's t test. Results: Increasing levels of IP were correlated with decreased arterial pH (p < 0.00003), increased mixed venous CO₂ (p < 0.003), decreased intramucosal pH (p < 0.014), and increased arterial CO₂ (p < 0.015). Gastric pH_i differed significantly from baseline at IP levels of 16 mm Hg (p < 0.004) and 18 mm Hg (p < 0.01). No significant effects were observed on cardiac output or arterial lactate. No significant effects were observed in a control group that had been insufflated to 8 mm Hg and held constant over 3 h. Conclusions: In this model, gastric blood flow is adversely affected by increasing IP with pronounced effects in excess of 15 mm Hg. These results suggest that gastric tonometry may be used to monitor the adverse effects of pneumoperitoneum. Gastric pH_i may be an earlier indicator of altered hemodynamic function during laparoscopy than traditional measures. Received: 25 March 1997/Accepted: 30 June 1997     

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     

Hemodynamic changes in the inferior caval vein during pneumoperitoneum

Background: Laparoscopic procedures of increasing difficulty and duration are becoming more and more common. This may cause significant challenges to the circulatory system and possibly influence thrombogenicity. Methods: Experimental study of carbon dioxide pneumoperitoneum in pigs. Results: Inferior caval vein blood flow remained unchanged, whereas inferior caval vein pressure increased during pneumoperitoneum. Inferior caval vein, pulmonary, and systemic vascular resistance increased during pneumoperitoneum and remained increased after exsufflation. Conclusions: Pneumoperitoneum leads to an increased inferior caval vein pressure, which could cause a dilation of peripheral veins. The similar patterns of vascular resistance in the inferior caval vein, pulmonary artery, and systemic arteries (a gradual increase remaining elevated after exsufflation) suggest a common humoral factor or increased sympathetic nerve activity. Received: 2 April 1996/Accepted: 7 June 1996     

Effects of laparoscopic vs laparotomy treatment of E. coli peritonitis on hemodynamic responses in a porcine model

Background: Laparoscopic surgery is being used now for increasingly diverse clinical applications, including diagnosis and treatment of appendicitis and bacterial peritonitis. However, some concerns and controversies exist regarding the effectiveness of laparoscopic irrigation of the abdominal cavity compared with that achieved during laparotomy. Of no less importance is concern that establishing a CO₂ pneumoperitoneum in patients with cardiopulmonary insufficiency or endotoxemic shock may compromise hemodynamic function. The objective of this randomized, controlled study was to determine the effects of laparoscopic versus laparotomy intervention on hemodynamic and outcome measurements using a porcine model of Escherichia coli peritonitis. Methods: For this study, 24 specific pathogen-free Hanford pigs underwent surgical placement of carotid, Swan-Ganz, and peritoneal catheters. After a 24-h recovery period, one subset of pigs (n= 12) received a bolus infusion of 9 × 10⁸ CFU/kg E. coli intraperitoneally (septic) and intravenous fluid resuscitation. The remaining 12 pigs were not challenged with E. coli (control). Twenty-four hours later, all 24 pigs underwent either laparoscopic or open peritoneal irrigation with saline, then were reevaluated 48 h after surgical intervention. Standard cardiopulmonary, hematologic, and bacteriologic assessments were obtained both perioperatively and 48 h after surgical intervention. Results: Pigs given E. coli exhibited significantly elevated heart rates and core temperatures and decreased O₂ saturation during the initial 6 h. Within 24 h, these pigs exhibited respiratory alkalosis, altered blood leukocyte profiles, and E. coli–infected peritoneal fluid. Random blood samples from the septic pigs tested negative for E. coli. Mean pulmonary artery and capillary wedge pressures were lower (p < 0.05) in septic than in control pigs before and after surgical intervention. Septic pigs that underwent laparoscopy had significantly lower (p < 0.05) arterial pH and higher arterial pCO₂ levels than septic pigs after laparotomy. Other cardiopulmonary responses were similar irrespective of the surgical modality used. One of six septic pigs from each surgical group still had E. coli growth in its peritoneal fluid 48 h after surgical intervention. Conclusion: Laparoscopic intervention demonstrated effectiveness equal to that of laparotomy for treating acute E. coli peritonitis in pigs without septic shock. Received: 26 June 1998/Accepted: 12 January 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     

Laparoscopic cholecystectomy and time-course changes in renal function

Background: Recently, the retraction method has been used to reduce intraabdominal pressure (IAP) during laparoscopic surgery. The purpose of this study was to determine the serial changes in renal function during laparoscopic cholecystectomy (LC) using the retraction method. Methods: Urine output, effective renal plasma flow (ERPF), and glomerular filtration rate (GFR) were measured serially in seven patients who underwent LC with 12 mmHg pneumoperitoneum (High-IAP group) and five who underwent LC using the retraction method with 4 mmHg pneumoperitoneum (Low-IAP group). Results: Urine output, ERPF, and GFR were decreased during pneumoperitoneum in the High-IAP group, whereas no significant changes in any of these parameters were observed in the Low-IAP group. Conclusions: Our findings demonstrate that reduction of IAP to 4 mmHg using the retraction method prevents the transient renal dysfunction caused by prolonged 12 mmHg pneumoperitoneum during LC, suggesting that the retraction method reduces the risk of perioperative renal dysfunction during laparoscopic surgery. Received: 26 March 1996/Accepted: 27 July 1996     

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     

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     

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 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     

Hepatic cryosurgery via minilaparotomy in a porcine model

Background: Cryosurgery of liver lesions is becoming increasingly accepted for the ablation of liver tumors. Attempts at laparoscopic cryosurgery have been very limited and often need to be converted to open laparotomy due to the complexity of the procedure. Methods: Seven domestic pigs were anesthetized, and 17 small (0.7 cm mean diameter) tumor mimicking agar ``lesions' were percutaneously placed in the liver. Two small subcostal incisions (∼2.0 cm) were placed, and an endocavitary ultrasound transducer (with a 2.4-mm cryoprobe mounted on it) was placed on the liver surface. Lesions were localized and directly punctured with one or two cryoprobes under ultrasound guidance, and a single 15-min freeze was undertaken. The animals were then killed, and their livers were removed and serially sectioned. Results: Total time for probe placement was approximately 10 min after incisions had been made. Animals tolerated the procedure well and all survived until they were killed. No intraabdominal complications were detected at exploration. Mean cryolesion dimensions were 3.0 cm (single probe) and 3.3 cm (dual probe) (p > 0.05). Positive margins were detected in one lesion treated with a single probe, and in none of the lesions treated with dual probes. Mean margins were 0.9 cm: 1.2 cm for the single probe and dual probe techniques, respectively. Liver surrounding control agar lesions demonstrated a thin rim of necrosis, approximately 0.5 mm wide. Conclusions: We conclude that minilaparotomy is an effective, safe, and simple method for performing hepatic cryosurgery in this animal model. This minimally invasive technique may benefit a subset of patients with lesions in accessible locations. Lesions in posterior locations may not be as amenable to this technique due to deterioration of ultrasound image quality in the far field. Received: 10 December 1997/Accepted: 27 March 1998     

Pneumoperitoneum risk prognosis and correction of venous circulation disturbances in laparoscopic surgery

Background: This study was initiated to find a method of determining the prognosis for possible changes in hemodynamic and respiratory parameters in patients with pneumoperitoneum (PP). Methods: We devised a model for a pseudopneumoperitoneum (PPP), which is created by encircling the wide pneumochamber on the entire abdomen and inflating it to a preset pressure. To verify the prognostic possibilities of the proposed model, we studied the pneumotachygraphy parameters, noninvasive and invasive monitoring parameters of PPP after induction of anaesthesia, and venous circulation disturbances, as well as the medical effect of the intermittent sequential compression device. Results: In healthy patients, the restrictive lung syndrome did not approach the risky limit. In patients ≥60 years old, this syndrome was very close to the limit. In a number of patients with serious cardiovascular and pulmonary pathology, the pressure of >10 mmHg was considered to be intolerable. Lung compliance, which was the parameter most sensitive to the increased intraabdominal pressure, was 47 ± 10 at baseline, and 29 ± 4 (p > 0.05) at both PPP and real PP (14 mmHg). Conclusions: The PPP model is quite similar to the real PP and can be used for preoperative prognosis in laparoscopic surgery. The elevated intraabdominal pressure results in a significant disturbance of venous blood flow in the lower extremities. The use of the device for peristaltic pneumomassage of the lower limbs is effective in correcting negative changes in venous hemodynamics in laparoscopic surgery. Received: 28 July 1997/Accepted: 12 January 1998     

Evaluation of the effects of a pneumoperitoneum with carbon dioxide or helium in a porcine model of endotoxemia

Background: The expansion of the laparoscopic techniques to the critically ill patient is currently under debate. In order to evaluate the potential risks of performing laparoscopy in a body with signs of sepsis, the effects of the pneumoperitoneum were studied in a porcine model of mild endotoxemia. Methods: Twenty-eight pigs were separated into four groups of seven animals: untreated control (C), 2 μg/kg/h endotoxin (E), endotoxin and a pneumoperitoneum (3 h, 15 mmHg) with CO₂ (EC) or with helium (EH). Hemodynamic and homeostatic variables were studied for a period of 5.5 h. Primary endpoints were arterial and mucosal pH and the ATP content of the bowel wall. Statistical evaluation was performed using analysis of variance and the Bonferroni test. Results: Endotoxin infusion induced characteristic symptoms of early sepsis: increase of arterial CO₂, pulmonary arterial, portal venous, and pulmonary artery wedge pressure, and decrease of arterial pressure, cardiac output, arterial and mucosal pH. An additional pneumoperitoneum led to aggravation of all criteria with significant alterations in arterial and mucosal pH, arterial CO₂, wedge and portal venous pressure. The most striking derangement of mean values was observed for mucosal pH (EC: 7.40, EH: 7.54) and arterial pH (EC: 7.15, EH: 7.18). In group EC, two animals died in septic shock. Conclusion: Applying a pneumoperitoneum during an ongoing sepsis significantly deteriorates hemodynamic and homeostatic variables, thus enhancing the risk of severe complications. Received: 26 July 1999 In revised form: 21 January 2000 Accepted: 24 January 2000     

Effects of laparotomy vs pneumoperitoneum on the hepatic catabolic stress response in ambulatory and stationary settings in pigs

Background: We recently demonstrated that laparoscopic cholecystectomy is followed by a much smaller hepatic catabolic stress response than conventional cholecystectomy. It is not known what is responsible for this difference. Methods: Thirty pigs were randomly allocated to the following five treatment groups: (1) laparotomy, (2) pneumoperitoneum, (3) pneumoperitoneum with insertion of four trocars, (4) laparotomy, (5) pneumoperitoneum. Groups 1–3 were operated on in an ambulatory setting, whereas groups 4 and 5 were operated on in a stationary setting. Urea synthesis, as quantified by functional hepatic nitrogen clearance, and the response of stress hormones and cytokines were assessed. Results: Laparotomy increased the functional hepatic nitrogen clearance by 195% (p < 0.001); pneumoperitoneum and trocars increased it by 145% (p < 0.001); and pneumoperitoneum alone increased it by 113% (p < 0.001). The difference between laparotomy and both pneumoperitoneum groups was significant. If the stress factor of ambulatory surgery was eliminated, the increase in functional hepatic nitrogen clearance was reduced to 87% (p < 0.01) after laparotomy and 38% (NS) for animals subject to pneumoperitoneum. There were significant differences in concentrations of stress hormones, tumor necrosis factor α, and interleukin 8 among groups intra- and postoperatively. Conclusions: The magnitude of the postoperative hepatic stress response after laparotomy compared to pneumoperitoneum with and without insertion of trocars seems to be caused by the greater trauma to the abdominal wall. Furthermore, an ambulatory setting seems to be an important postoperative stress factor in itself. Received: 28 April 1998/Accepted: 18 August 1998     

A pneumoperitoneum perpetuates severe damage to the ultrastructural integrity of parietal peritoneum in gastric perforation-induced peritonitis in rats

Background: Minimal invasive surgery is increasingly used in conditions complicated by peritonitis—e.g., peptic ulcer perforation. This study was devised to assess the effect of a pneumoperitoneum (PP) on the ultrastructural integrity of parietal peritoneum in perforation-induced peritonitis. Methods: Anesthetized rats were subjected either to standardized gastrotomy simulating gastric perforation (groups Ia–d; IIa–d) or to sham perforation (groups IIIa–d, IVa–d). In group I (a–d) and III (a–d), CO₂ was insufflated 12 h after gastrotomy for 60 min (P_ia 4 mmHg). Glutaraldehyde was administered intraperitoneally at the end of the PP period while the abdominal wall was still extended (group index a), as well as 30 sec (b), 2 h (c), and 12 h (d) after desufflation. Specimens were taken from the parietal peritoneum of the left diaphragm for scanning electronic-microscopic (SEM) analysis. In groups II (a–d) and IV (a–d), simple puncture of the abdominal cavity was performed, and specimens were taken at corresponding times. Results: In group Ia (gastric perforation with PP), distortion of the mesothelial cell layer with concomittant opening of stomata to the submesothelial tissue was already observed in specimens harvested while the abdominal wall was still extended. Concomitantly, scarce microvilli, which appeared coarse and thickened, were lying flat on top of the mesothelial cells. After desufflation (groups Ib–c), a rapid process of mesothelial disintegration with disruption from the submesothelial layer and vanishing of microvilli occurred. At 12 h after PP (group Id), complete deterioration of mesothelial cell integrity was observed. In groups IIa–c (gastric perforation without PP), microvilli appeared shrunk and coarse, while integrity of the mesothelial cell layer remained intact up to 2 h after the abdominal puncture. At 12 h after abdominal puncture (group IId), the microvilli had nearly completely vanished and the mesothelium was breaking apart into multiple soils. Conclusions: In SEM analysis of parietal peritoneum, premature distortion, and disintegration of the mesothelial cell layer was observed in animals exposed to increased abdominal pressure in addition to gastric perforation-induced peritonitis. Received: 4 May 1998/Accepted: 17 November 1998     

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