Mechanism of decreased in vitro murine macrophage cytokine release after exposure to carbon dioxide: relevance to laparoscopic surgery.

OBJECTIVE: The objective of this study was to determine the effect of carbon dioxide (CO2) on the function of peritoneal macrophages. SUMMARY BACKGROUND DATA: Laparoscopic surgery is associated with minimal pain, fever, and low levels of inflammatory cytokines. To understand the mechanisms involved, the authors investigated the effect of different gases on murine peritoneal macrophage intracellular pH and correlated these alterations with alterations in LPS-stimulated inflammatory cytokine release. METHODS: Peritoneal macrophages were incubated for 2 hours in air, helium, or CO2, and the effect of the test gas on immediate or next day lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) and interleukin-1 release compared. Cytosolic pH of macrophages exposed to test gases was measured using single-cell fluorescent imaging. The in vivo effects of test gases were determined in anesthetized rats during abdominal insufflation. RESULTS: Macrophages incubated in CO2 produced significantly less TNF and interleukin-1 in response to LPS compared to incubation in air or helium. Cytokine production returned to normal 24 hours later. Exposure to CO2, but not air or helium, caused a marked cytosolic acidification. Pharmacologic induction of intracellular acidification to similar levels reproduced the inhibitory effect. In vitro studies showed that CO2 insufflation lowered tissue pH and peritoneal macrophage LPS-stimulated TNF production. CONCLUSIONS: The authors propose that cellular acidification induced by peritoneal CO2 insufflation contributes to blunting of the local inflammatory response during laparoscopic surgery.     

Abdominal insufflation with CO2 causes peritoneal acidosis independent of systemic pH.

We have shown that the inflammation-attenuating effects of CO(2) pneumoperitoneum during laparoscopy are not due to changes in systemic pH. However, acidification of peritoneal macrophages in an in vitro CO(2) environment has been shown to reduce LPS-mediated cytokine release. We tested the hypothesis that the peritoneum is locally acidotic during abdominal insufflation with CO(2)--even when systemic pH is corrected. Rats (n = 20) were anesthetized and randomized into two groups: continued spontaneous ventilation (SV) or intubation and mechanical ventilation (MV). All animals were then subjected to abdominal insufflation with CO(2). Mean arterial pH among SV rats decreased significantly from baseline after 15 and 30 minutes of CO(2) pneumoperitoneum (7.329 --> 7.210 --> 7.191, P < 0.05), while arterial pH among MV rats remained relatively constant (7.388 --> 7.245 --> 7.316, P = NS). In contrast, peritoneal pH dropped significantly from baseline and remained low for both groups during CO(2) abdominal insufflation (SV 6.74 --> 6.41 --> 6.40, P < 0.05; MV 6.94 --> 6.45 --> 6.45, P < 0.05). In a second experiment, rats (n = 10) were randomized to receive abdominal insufflation with either CO(2) or helium. Abdominal insufflation with helium did not significantly affect peritoneal pH (7.10 --> 7.02 --> 6.95, P = NS), and the decrease in pH among CO(2)-insufflated animals was significant compared with helium-insufflated animals (P < 0.05). Peritoneal pH returned to baseline levels in all groups within 15 minutes of desufflation in both experiments. A significant local peritoneal acidosis occurs during laparoscopy which is specifically attributable to the use of CO(2) and which is independent of systemic pH. These data provide additional evidence that localized peritoneal acidosis is central to the mechanism of CO(2)-mediated attenuation of the inflammatory response following laparoscopic surgery.     

腹膜后腹腔镜手术对全麻患者呼吸及循环的影响

目的:了解腹膜后腹腔镜手术对全麻患者呼吸及循环的影响。方法:选择60例患者择期行腹膜后腹腔镜泌尿外科手术,ASAⅠ～Ⅱ级。观察气腹前、气腹后30、60、90min的MAP、HR、pH、PaCO2、PETCO2、Pa-PETCO2的变化。结果:气腹后患者MAP和HR无显著变化(P>0.05),气腹后较气腹前pH降低,PaCO2、PETCO2、Pa-PETCO2升高(P<0.05),气腹后各时间点以上指标无显著差异(P>0.05)。结论:气腹后PaCO2、PETCO2上升,pH下降,但不呈进行性的变化。     

Peritoneal acidosis mediates immunoprotection in laparoscopic surgery

BACKGROUND: We have shown previously that abdominal insufflation with CO(2) increases serum levels of IL-10 and TNFalpha and increases survival among animals with lipopolysaccharide (LPS)-induced sepsis, even after a laparotomy. We demonstrated previously that the effect of CO(2) is not from changes in systemic pH, although the peritoneum is locally acidotic during abdominal insufflation with CO(2) even when systemic pH is corrected. We hypothesized that acidification of the peritoneum via means other than CO(2) insufflation would produce alterations in the inflammatory response similar to those associated with CO(2) pneumoperitoneum. METHODS: In total, 42 rats were randomized into 7 groups (n = 6): 1) LPS only, 2) anesthesia control, 3) helium pneumoperitoneum, 4) CO(2) pneumoperitoneum, 5) buffered mild acid lavage, 6) buffered strong acid lavage, and 7) buffered strong acid lavage + helium pneumoperitoneum. Animals received anesthesia with vaporized isoflurane (except the LPS-only group) and their respective abdominal treatment (pneumoperitoneum and/or lavage) for 30 min followed immediately by stimulation with systemic LPS (1 mg/kg, IV). Blood was harvested via cardiac puncture 60 min after LPS injection, and serum levels of IL-10 and TNFalpha levels were determined by enzyme-linked immunosorbent assay. RESULTS: Mean peritoneal pH decreased (P < .05) after CO(2) pneumoperitoneum, buffered strong acid lavage, and buffered strong acid lavage + helium pneumoperitoneum, and it decreased (P = .1) after helium pneumoperitoneum alone and buffered mild acid lavage. IL-10 levels were increased (P < .01), and TNFalpha levels decreased (P < .001) among animals with acidic peritoneal cavities compared with animals with pH-normal peritoneal cavities. Decreasing peritoneal pH correlated with both increasing IL-10 levels (r = -.465, P < .01) and decreasing TNFalpha levels (r = 0.448, P < .01). Among animals with peritoneal acidosis, there were no differences in levels of IL-10 or TNFalpha regardless of insufflation status (P > .05 for both cytokines). CONCLUSIONS: Acidification of the peritoneal cavity whether by abdominal insufflation or by peritoneal acid lavage increases serum IL-10 and decreases serum TNFalpha levels in response to systemic LPS challenge. The degree of peritoneal acidification correlates with the degree of inflammatory response reduction. These results support the hypothesis that pneumoperitoneum-mediated attenuation of the inflammatory response after laparoscopic surgery occurs via a mechanism of peritoneal cell acidification.     

Impact of carbon dioxide and helium insufflation on cardiorespiratory function during prolonged pneumoperitoneum in an experimental rat model

BACKGROUND: Experimental studies on laparoscopic surgery are often performed in rats. However, the hemodynamic and respiratory responses related to the pneumoperitoneum have not been studied extensively in rats. Therefore, the aim of this study was to investigate in spontaneously breathing rats the effects of CO2 and helium, insufflation pressure, and duration of pneumoperitoneum on blood pressure, arterial pH, pCO2, pO2, HCO3-, base excess, and respiratory rate. METHODS: Five groups of 9 Brown Norway rats were anesthetized and underwent CO2 insufflation (6 or 12 mmHg), helium insufflation (6 or 12 mmHg), or abdominal wall lifting (gasless control) for 120 min. Blood pressure was monitored by an indwelling carotid artery catheter. Baseline measurements of mean arterial pressure (MAP), respiratory rate, arterial blood pH, pCO2, pO2, HCO3-, and base excess were recorded. Blood gases were analyzed at 5, 30, 60, 90, and 120 min during pneumoperitoneum, and MAP and respiratory rate were recorded at 5 and 15 min and at 15-min intervals thereafter for 2 h. RESULTS: CO2 insufflation (at both 6 and 12 mmHg) caused a significant decrease in blood pH and increase in arterial pCO2. Respiratory compensation was evident since pCO2 returned to preinsufflation levels during CO2 insufflation at 12 mmHg. There was no significant change in blood pH and pCO2 in rats undergoing either helium insufflation or gasless procedures. Neither insufflation pressure nor the type of insufflation gas had a significant effect on MAP over time. CONCLUSION: The cardiorespiratory changes during prolonged pneumoperitoneum in spontaneously breathing rats are similar to those seen in clinical practice. Therefore, studies conducted in this animal model can provide valuable physiological data relevant to the study of laparoscopic surgery.     

腹腔镜与后腹腔镜CO2气腹对患者血流动力学及血气的影响

【摘要】目的 探讨经腹腔和经腹膜后腔入路手术CO2气腹对患者血流动力学及血气的影响。 方法 选择经腹腔和经腹膜后腔入路手术患者各50例,监测气腹前、气腹后30min、60min和气腹结束后30min血流动力学和动脉血气的变化。 结果 两组患者组内气腹后30min、60min患者心率(HR)、平均动脉压（MAP）、中心静脉压（CVP）均较气腹前有显著性差异（P<0.05）。组间比较无差异（P>0.05）。两组患者组内气腹后30、60min患者动脉血二氧化碳分压（PaCO2）较气腹前明显增加,pH明显下降（P<0.05）。组间比较腹膜后腔组变化更明显（P<0.05）。结论 经腹膜后腔入路手术CO2气腹对患者血流动力学和动脉血气的影响更大,术中需加强呼吸管理和内环境监测。     

Impact of laparoscopic gases on peritoneal microenvironment and essential parameters of cell function

Several experimental studies confirm the hypotheses that laparoscopic gases influence the development of tumor metastases [12, 14, 23]. The mechanism for this alteration of malignant tumor growth is still unknown. One reason might be an influence of the in sufflation gas on essential cell function regulating parameters. To investigate the changes of the intra- and extracellular milieu, four parameters—extra- and intracellular pH, intracellular free calcium levels, and tissue oxygen partial pressure—were measured during insufflation with carbon dioxide (CO2), helium (He), or a nonhypoxic gas mixture consistent of 80% CO2 and 20% O2. Study design (In vitro experiments) Intracellular calcium and pH levels were measured in DHD/K12/TRb colon adenocarcinoma cells using fluorescence imaging microscopy. (In vivo experiments) Tissue oxygen partial pressure was measured using a flexible micro catheter (Licox CMP) implanted in the abdominal wall of rats. After establishing the pneumoperitoneum an optical system and an aspirator were inserted to control the position of the micro catheter and to aspirate wound exudates for pH measurements of the wound fluid. Results: Creating of pneumoperitoneum with both CO2 and helium caused a decrease in partial pressure of oxygen in the abdominal wall to about 5 mm Hg whereas insufflation with a nonhypoxic gas mixture (80% CO2 and 20% O2) induced no significant changes. The intra- and extra cellular pH values dramatically decreased during CO2 insufflation (7.4 to 6.2) in vitro. Helium caused a pH increase up to 7.6. Free intracellular calcium was enhanced during CO2 insufflation, whereas helium insufflation did not cause any changes in [Ca2+]i. Nevertheless, a significant decrease of [Ca2+]i was observed during reoxygenation following helium-induced hypoxia. Conclusion: Our study demonstrates that insufflation with either CO2 or He causes significant changes of intra- and extracellular parameters regulating essential cell functions such as oxidative phosphorylation to produce ATP, cell proliferation, or onset of apoptosis.     

Liver blood flow changes during laparoscopic surgery in pigs

BACKGROUND: Physiological effects caused by abdominal insufflation in the course of laparoscopic surgery are partially unknown. The purpose of the present study was to determine if indocyanine green (ICG) pharmacokinetic parameters, as an index of hepatic blood flow, change during laparoscopic surgery in the presence of a CO2 pneumoperitoneum. This effect could cause important alterations in the kinetics of anesthetic drugs. METHODS: Eighteen female pigs were anaesthetized under constant ventilation and randomly assigned to three groups undergoing insufflation with CO2 (I), laparoscopic oophorectomy with CO2 pneumoperitoneum (LS), or oophorectomy by open surgery (OS). CO2 pneumoperitoneum was performed at 14 mmHg. ICG (1 mg/kg) was injected into a marginal vein on two separate occasions: 30 min before and 30 min after the start of insufflation or surgery. Blood was sampled from the carotid artery at time intervals after the injection of ICG and after pharmacokinetic parameters were obtained by a computer program. RESULTS: The area under the curve (AUC0-infinity) indicated important dysfunctions in ICG availability in all three groups of animals, with significant increases of 104%, 82%, and 48% for groups I, LS, and OS, respectively. The ICG apparent half-life did not significantly change in group OS, but it rose in groups I (+17%) and LS (+28%). ICG clearance was significantly reduced by 32% in group OS and to a larger extent in groups I and LS (-45% and -46%, respectively). CONCLUSION: These findings confirm the contribution of CO2 pneumoperitoneum to decreased liver blood flow during laparoscopic surgery.     

Macrophage-mediated bone resorption occurs in an acidic environment

Summary Resorption is a continuous skeletal process involving the degratation of both the organic and inorganic matrices of bone. This process has received much attention, but little is known about the physical mechanism by which resorptive cells degrade the skeleton. In this study, we examined the pH at the resorptive cell-bone interface using a fluorescent dye, fluorescein isothiocyanate, conjugated to the organic matrix of devitalized rat bone. Because the visible spectrum of fluorescein differs in acidic and neutral environments, the relative magnitudes of fluorescence at two different wave lengths indicates whether the pH at the fluorescing site is above or below the pKa of the dye. Our studies indicate that macrophage-mediated bone resorption occurs at pH below 6.0. The presence of parathyroid hormone or calcitonin, however, has no effect on the cell-matrix interface pH after 6 hours of incubation. In contrast to resorptive macrophages, fibroblasts, which bind to bone without resorbing it, do not generate an acidic environment at the matrix attachment site. This work was supported in part by NIH Grant No. AM32788 and by a Nenezian donation.     

Hemodynamic and respiratory effects of pediatric urological retroperitoneal laparoscopic surgery: a prospective study

PURPOSE: Our understanding of the effects of retroperitoneal CO(2) insufflation on cardiopulmonary variables in children remains limited. This study was designed to investigate prospectively the effect of CO(2) insufflation in a pediatric population undergoing retroperitoneal laparoscopic surgery. MATERIALS AND METHODS: We prospectively evaluated a consecutive series of patients enrolled between July 2003 and August 2004. Anesthesia was administered following a standardized protocol. Data collection included respiratory rate, PAP, O(2) saturation, ETCO(2), HR, MAP, electrocardiogram and insufflation pressure. All variables were recorded before, during and after CO(2) insufflation at regular intervals of 1 to 2 minutes, with up to 23 measurements recorded for each period. RESULTS: A total of 18 participants were recruited. Mean +/- SD for age and weight were 79.4 +/- 53.2 months and 26.7 +/- 15.5 kg, respectively. Mean retroperitoneal CO(2) insufflation pressure was kept at 12 mm Hg. Significant differences (p <0.05) in average ETCO(2), PAP and MAP were noted after CO(2) insufflation compared to baseline (pre-pneumoretroperitoneum) values. HR and temperature did not change. At completion of the laparoscopic intervention physiological variables exhibited a trend to return to baseline values. CONCLUSIONS: This prospective study documents significant changes in systemic hemodynamic variables that seem to be directly associated with the insufflation of CO(2) during pediatric retroperitoneal laparoscopic surgery. This ongoing evaluation confirms the effect of laparoscopic urological surgery and CO(2) insufflation on cardiopulmonary function in children.     

Carbon dioxide directly suppresses spontaneous migration, chemotaxis, and free radical production of human neutrophils

BACKGROUND: Carbon dioxide (CO(2)) insufflation during laparoscopy has been shown to dampen the systemic stress response to surgery. This is related to a suppression of peritoneal macrophage functions. In vivo data suggest that CO(2) can also affect neutrophils (polymorphonuclear cells, PMNs), the most abundant cell type in the inflamed peritoneal cavity. Nonetheless, the direct effects of CO(2) on PMNs have not yet been investigated. METHOD: PMNs were isolated from peripheral blood of healthy volunteers and incubated with (1) CO(2) (100% CO(2), pH 6.2), (2) hypoxic control (95% helium/5% CO(2), pH 7.4), and (3) control (95% air/5% CO(2), pH 7.4). Spontaneous and IL-8-induced migrations (chemokinesis and chemotaxis) during 2 h of exposure to different gases were measured with a transwell chamber system. The release of reactive oxygen species (ROS, luminometry) was determined after 15-min and 2-h exposures. In other sets of experiments, PMNs were exposed for 2 h or 4 h and kept under normal conditions for 18 h with lipopolysaccharide (LPS) stimulation thereafter. Final viability and apoptosis were assessed with fluorometry. RESULTS: Exposure to 100% CO(2) completely blocked spontaneous and IL-8 induced migration of PMNs (p < 0.001 vs. controls). Neutrophil migration was slightly diminished in the hypoxic control group. PMA-stimulated ROS production was reduced even after short exposure to 100% CO(2)(p < 0.05). We observed a slight increase of caspase-3/7 activity after exposure to 100% CO(2) and/or hypoxia; however, total viability was not affected. CONCLUSIONS: CO(2) incubation directly and temporarily suppresses the proinflammatory functions of PMNs; this is caused only partially by the concomitant hypoxia. This effect will contribute to the dampened inflammatory response to laparoscopic surgery. Further studies are needed to investigate whether the temporary suppression of neutrophil functions could affect the clearance of bacterial contaminations.     

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

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

Intraoperative Modulation of Alveolar Macrophage Function during Isoflurane and Propofol Anesthesia

Background: Alveolar macrophages are a critical part of the defense against pulmonary infection. Thus the authors determined time-dependent changes in alveolar macrophage functions in patients having surgery who were anesthetized with isoflurane or propofol.

Methods: Patients anesthetized with propofol (n = 30) or isoflurane (n = 30) during orthopedic surgery were studied. Alveolar macrophages were harvested by bronchoalveolar lavage immediately, and 2, 4, and 6 h after induction anesthesia and at the end of surgery. The fraction of aggregated and nonviable macrophages was determined. Then phagocytosis was measured by ingestion of opsonized and unopsonized particles. Finally, microbicidal activity was determined as the ability of the macrophages to kill Listeria monocytogenes directly.

Results: Demographic and morphometric characteristics of the patients given propofol and isoflurane were similar, as were their levels of pulmonary function and hemodynamic responses. The fraction of alveolar macrophages ingesting opsonized and unopsonized particles, and the number of particles ingested, decreased significantly over time, with the decrease slightly but significantly greater during isoflurane anesthesia. Microbicidal function decreased progressively during anesthesia and surgery, with the decrease almost twice as great during isoflurane compared with propofol anesthesia. The fraction of aggregated macrophages and recovered neutrophils increased over time in the patients given each anesthetic.     

Laparoscopic surgery with carbon dioxide insufflation causes respiratory acidosis.

This study analyzes the changes in cardiopulmonary parameters of patients undergoing laparoscopic cholecystectomy. Six healthy females with normal preoperative cardiopulmonary status were selected for laparoscopic surgery using the same criteria as for traditional cholecystectomy. Respiratory and cardiovascular parameters were collected and compared prior to peritoneal insufflation and just before desufflation. Patients experienced significant elevations of arterial and end-tidal CO2, accompanied by decreased pH. Bicarbonate concentration, blood pressure and pulse rate remained constant. Based on these results, and on our laboratory investigations, we have introduced helium as an alternate agent for insufflation, and present the data from the first two patients so managed. No change was observed in EtCO2, PaCO2 or pH in either of these two patients during the course of surgery. We conclude that hypercarbia occurs in those undergoing laparoscopic cholecystectomy with CO2 insufflation. This acidosis requires compensation by increased minute ventilation to prevent decline in pH. In our initial experience, helium did not produce these changes, and therefore merits further investigation as an alternate agent for abdominal insufflation.     

Influence of rBAT-mediated amino acid transport on cytosolic pH

rBAT, together with its subunit b(0,+) AT mediates the hetero- and homoexchange of neutral and dibasic amino acids. Since the heteroexchange of dibasic amino acids against neutral amino acids is coupled to net transport of positive charge, this transport is electrogenic. Extracellular addition of histidine could create an inward or an outward current depending on extracellular pH (pH(e)) and cell membrane potential. It has been concluded that histidine may be transported in both its protonated and its neutral form. In this study measurements of cytosolic pH (pH(i)) were performed to test this hypothesis. As a result, addition of protonated histidine at acidic pH(e) to Xenopus oocytes expressing rBAT creates an inward current which is paralleled by cytosolic acidification. Both can be reduced by increase of pH(e). At alkaline pH(e) and simultaneous depolarization of the cell membrane the effect of histidine on pH(i) is virtually abolished. The neutral amino acid leucine does not alter cytosolic pH at neither pH 6.0 nor at pH 8.0. In conclusion, histidine can be transported in either its neutral or its protonated form. Transport of the protonated form is facilitated by extracellular acidification and hyperpolarization of the cell membrane.     

Comparison of immune preservation between CO2 pneumoperitoneum and gasless abdominal lift laparoscopy.

OBJECTIVE: Carbon dioxide (CO2) pneumoperitoneum has been implicated as a possible factor in early immune preservation in laparoscopic surgery. Although the current analysis was not adequate to clarify this issue, the aim of this study was to compare CO2 insufflation laparoscopic cholecystectomy to gasless abdominal wall lift laparoscopic cholecystectomy with respect to preservation of the immune system. METHOD: An analysis of the temporal immune responses was performed in 2 similar groups of patients (n = 50) who were divided randomly into the categories of gas or abdominal wall lift laparoscopic cholecystectomy. The patients were matched with respect to age, weight, and operation time. The immune parameters (serum white blood cell count, cortisol, erythrocyte sedimentation rate [ESR], tumor necrosis factor-alpha [TNF-alpha], interferon-y [INF-gamma], interleukin-6 [IL-6], interleukin-8 [IL-8]) were assessed at preoperative 24 hours and at postoperative 24 and 72 hours for the 2 groups. During the operation, the levels of cytokines that were cultured in the peritoneal macrophages were also checked. RESULTS: The serum white blood cell count, cortisol, and ESR levels were not statistically different in either of the 2 groups. Further, the serum TNF-alpha, INF-gamma, IL-6, and IL-8 levels in both groups were not significantly different from each other at preoperative 24 hours, and postoperative 24 and 72 hours. However, an immediate decrease in the cytokine levels at 24 hours after the operation was significant in both groups. The cytokine levels were particularly higher in the cultured peritoneal macrophages than in the serum, but were not statistically different between the 2 groups. CONCLUSION: Our results showed that the beneficial immune response obtained in the CO2 gas insufflation laparoscopic procedure could also be obtained in the gasless abdominal wall lift laparoscopic procedure. An immediate preservation of the immune functions in the postoperative period was detected similarly in the 2 groups.     

Oncological effects of insufflation with different gases and a gasless procedure in rats

Background: The validity of using carbon dioxide (CO₂) pneumoperitoneum in laparoscopic tumor surgery has not been investigated thoroughly. The oncologic effects of a gasless procedure and insufflation with different gases were compared in rats. Methods: In all the experiments, Donryu rats were randomized to receive a gasless procedure; to receive insufflation with CO₂, helium, or air at 10 mmHg for 30 min, or to serve as control subjects without insufflation. In experiment 1, involving 60 rats, ascites hepatoma AH130 cells were inoculated intraperitoneally just before the procedures. The S-phase fraction of the intraperitoneal tumor cells was determined using a flow cytometry on day 7. In experiment 2, 60 rats injected intraperitoneally with latex particles received one of the procedures. At the end of the procedure, peritoneal macrophages were harvested to determine the number of phagocytosed particles. In experiment 3, 75 rats inoculated intraperitoneally with AH130 cells received one of the procedures for 5 consecutive days and were followed for survival analysis. Results: Experiment 1: The S-phase fraction was lower after insufflation with air or helium (p < 0.01) than with the anesthesia control condition. Insufflation with CO₂ showed a higher S-phase fraction than the gasless procedure or insufflation with air or helium ( p < 0.01). Experiment 2: The phagocytotic activity of peritoneal macrophages was increased by insufflation with helium and air, as compared with the control condition ( p < 0.01). Insufflation with CO₂ deteriorated the phagocytotic activity more than the gasless procedure ( p < 0.05) or insufflation with air or helium ( p < 0.001). Experiment 3: Insufflation with gases demonstrated shorter survival than the anesthesia control condition or the gasless procedure regardless of the gases used (p < 0.01). Conclusions: These results suggest that the choice of gases may affect the proliferation of tumor cells and the phagocytotic activity of peritoneal macrophages, insufflation itself may promote tumor spread regardless of the gases used, and the gasless procedure may be oncologically advantageous in this animal model.     

Arterial to end-tidal carbon dioxide tension difference during laparoscopic colorectal surgery

BACKGROUND: Determination of end-tidal carbon dioxide pressure (PET(CO2)) is effective to confirm adequate ventilation, because arterial to end-tidal carbon dioxide tension difference (deltaa-ET(CO2)) does not change normally during operation. But deltaa-ET(CO2) may change during laparoscopic surgery, because peritoneal insufflation of CO2 will increase CO2 production and reduce functional residual volume. Changes in deltaa-ET(CO2) were reported in laparoscopic cholecystectomy with cardiovascular complication, but there is controversy about how deltaaET(CO2) will change in more complicated and long laparoscopic surgery. In this prospective study, we examined changes in deltaa- ET(CO2) during laparoscopic colorectal surgery. METHODS: Fifty patients received combined general and epidural anesthesia. CO2 pneumoperitoneum was initiated after obtaining arterial blood for gas analysis. Mechanical ventilation was used to maintain PET(CO2) at a stable value between 30 and 40 mmHg during the procedure. Arterial blood gas analysis was performed 10, 60, 120 minutes after CO2 insufflation, and 10 minutes after the termination of insufflation. RESULTS: The mean +/- SD for deltaa-ET(CO2) was 5.8 +/- 4.1 before pneumoperitoneum, 7.1 +/- 4.8, 8.1 +/- 5.4, 6. 4 +/- 4.9 in 10, 60, 120 minutes after pneumoperitoneum, and 6.4 +/- 4.9 in 10 minutes after the termination of pneumoperitoneum. deltaa-ET(CO2) increased significantly during pneumoperitoneum, but did not increase further even if CO2 insufflation was longer than 60 minutes. CONCLUSIONS: In laparoscopic colorectal surgery, Pa(CO2) should be checked for at least the first 60 minutes to confirm adequate ventilation.     

Acidification during carbon dioxide pneumoperitoneum is restricted to the gas-exposed peritoneal surface: effects of pressure, gas flow, and additional intraperitoneal fluids

BACKGROUND: There are varying data regarding the degree and extent of abdominal acidification during laparoscopy. The aim of this study was to determine the extent of peritoneal acidification during carbon dioxide insufflation and the effects of different pressures, insufflation rates, and free intraperitoneal fluids. MATERIALS AND METHODS: Sixteen male Sprague-Dawley rats weighing 250-300 g were anesthetized and a two-point pH probe was inserted in the abdominal cavity. After closure of the abdominal wall, each group of 4 rats was subjected to one of four insufflation regimens: low pressure (2 mm Hg, no leakage); high pressure (10 mm Hg, no leakage); leakage (2 mm Hg, leakage 0.5 mL/min); and fluid (2 mm Hg, 10 mL intraperitoneal 0.9% NaCl). During insufflation peritoneal pH was continuously measured. RESULTS: Carbon dioxide insufflation significantly decreased the peritoneal pH to <7.0 only in areas exposed to the insufflation gas. Neither changes in pressure nor insufflation rate had major effects on the peritoneal pH. The addition of 10 mL normal saline into the abdominal cavity significantly enhanced the pH change during insufflation. conclusion: Acidification associated with carbon dioxide pneumoperitoneum is limited to the area of inspection and manipulation. The increased acidification following injection of normal saline could offer a useful mechanism to alter the inflammatory response.     

"Low-pressure" laparoscopic cholecystectomy in high risk patients (ASA III and IV): our experience

The insufflation pressure used for laparoscopic cholecystectomy is usually 12-15 mm Hg, and a pneumoperitoneum with carbon dioxide has a significant effect on both cardiovascular and respiratory function. These effects are transient in young, healthy patients, but may be dangerous in ASA III and IV patients with a poor cardiac reserve. This study was designed to assess the feasibility of performing laparoscopic cholecystectomy at 6.5-8 mm Hg insufflation pressure in "high-risk" patients. Thirteen patients, 10 ASA III and 3 ASA IV, with cholelithiasis, were included in this study The insufflation pressure was 6.5-8 mm Hg, with a 10 degrees anti-Trendelenburg position. The cardiovascular and blood gas variables studied were: mean arterial blood pressure, heart rate, respiratory rate, and end-tidal CO2 pressure. The authors reported no conversions and no intra- or postoperative complications. During insufflation heart rate and mean arterial blood pressure increased minimally if compared with laparoscopic cholecystectomy at 12-15 mm Hg. Pa CO2 increased after insufflation (+5 mm Hg), and the end-tidal CO2 pressure gradient was moderate (3.5 mm Hg) and unchanged during surgery. A low-pressure pneumoperitoneum is feasible for laparoscopic cholecystectomy and minimizes the adverse haemodynamic effects of peritoneal insufflation.