INTRODUCTION

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DURING LAPAROSCOPIC PROCEDURES abdominal organs are visualized by intraperitoneal insufflation of gas (mostly CO₂). To facilitate access to organs in the upper or lower part of the abdomen, the pneumoperitoneum is combined with head-up or head-down tilts. Despite the hemodynamic and respiratory consequences of increased intra-abdominal pressures (IAP), laparoscopic surgery has been found to offer several advantages such as reduced postoperative pulmonary dysfunction and short hospitalization time (27-29). If for many years, gynecologic laparoscopy was performed mainly in young, healthy patients, this technique is now applied in general surgery for various and long-lasting operations and involves older patients suffering from patent or unknown diseases. Therefore, the consequences of elevated IAP and changes in position may increase the morbidity rate of these patients.

Although ventilatory and hemodynamic changes during surgical laparoscopy have been extensively investigated in humans, little information is available on hepatic blood flow during the procedure. The consequences of IAP increase on hepatic blood flow have already been studied in various experimental models. In anesthetized pigs, Diebel et al. showed that a 20-mmHg increase in IAP (induced by fluid infusion in the abdomen) decreased hepatic (5) as well as mesenteric (4) perfusion. In contrast, in anesthetized dogs, increasing IAP up to 20 mmHg by CO₂ insufflation did not compromise mesenteric blood flow (16). When IAP was increased by inflating a large bag into the peritoneum hepatic artery blood flow (HABF) increased, but this increase was not sufficient to maintain total hepatic blood flow (THBF) (21). The consequences of various positions such as head-down and head-up tilts on hepatic blood flow are also unknown. Moreover, hypercapnia, ventilation with high tidal volume, and anesthetic agents may also interfere with hepatic blood flow during surgical laparoscopy. The aim of the present study was to investigate the modifications of hepatic blood flow after CO₂ insufflation and changes of tilt in anesthetized pigs.

	METHODS

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Animals and anesthesia. Male or female domestic pigs (21-28 kg, n = 9) were fasted with free access to water for 24 h before the experiment, premedicated, and placed in a supine position on the operating table with the front- and hindlimbs fixed in the abduction position. After induction of anesthesia with halothane, pigs were intubated and mechanically ventilated with air and O₂ (fractional inspired O₂ = 0.4) to obtain normal arterial pH and arterial PCO₂ (Pa_CO2) between 36 and 42 mmHg. After intubation, halothane was withdrawn and anesthesia was maintained with thiopental (5 mg · kg¹ · h¹) and fentanyl (10-20 µg · kg¹ · h¹). Pancuronium (0.2 mg · kg¹ · h¹) was used as a skeletal muscle relaxant. The protocol was approved by the Animal Welfare Committee of the University of Geneva and the Veterinary Office and followed the Guidelines for the Care and Use of Laboratory Animals.

Surgical procedure. The right carotid artery was cannulated to measure mean arterial pressure (MAP, mmHg) and to collect blood samples. A catheter was inserted into the right external jugular vein to provide fluid and drugs. A pulmonary artery catheter (131H-7F, Baxter, Düdingen, Switzerland) was inserted through the right internal jugular vein to measure mean pulmonary arterial pressure (MPAP, mmHg), central venous pressure (CVP, mmHg), pulmonary capillary wedge pressure (PCWP, mmHg), and cardiac output (l/min).

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Experimental protocol. After the animals were anesthetized and instrumented, a 2-h recovery period was observed for the stabilization of hemodynamic and biologic variables. Under stable anesthesia, respiratory and hemodynamic measurements were performed in the horizontal position, with 10 and 20° head-down and 10 and 20° head-up tilts. Variables were allowed to stabilize for 5 min before data collection. Thereafter, to create the pneumoperitoneum, intra-abdominal CO₂ was insufflated through a Verres needle by an automatic insufflator (26012, Storz, Tuttligen, Germany). CO₂ was insufflated in the horizontal position until IAP reached ~15 mmHg. Measurements were then repeated in the five different positions. Head-down and head-up tilts were randomized, whereas the amplitude of tilt was not. Data were collected in the horizontal position after the recovery period (H1), after head-down and head-up tilts (H2 and H3), after CO₂ insufflation (H4), after head-down and head-up tilts during pneumoperitoneum (H5 and H6), and after CO₂ exsufflation (H7). During the protocol, minute ventilation was adjusted to obtain normal PCO₂ by increasing tidal volume. A tilt of 20° and an IAP increase of 15 mmHg were chosen because we wanted to mimic the tilt and IAP increase commonly used in clinical laparoscopy.

Systemic and hepatic oxygenation. Expired flow from the ventilator was directly connected to a metabolic measurement cart (Datex, Helsinki, Finland) for continuous measurements of O₂ consumption (O₂, ml/min) and CO₂ production (CO₂, ml/min). O₂ contents in the carotid artery, the portal vein, and the hepatic vein were determined in blood samples obtained from the appropriate catheters and analyzed for PO₂, Hb concentration, and fractional O₂ saturation (SO₂).

Statistical analysis. All results were expressed as means ± SE. Data were analyzed using repeated-measures analysis of variance followed by a Scheffé's test to compare mean values. P < 0.05 was considered significant.

	RESULTS

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CO₂ variables. CO₂ variables are given in Table 1. Minute ventilation was adjusted to obtain normal blood gases during CO₂ insufflation as described in METHODS, and consequently Pa_CO2 and end-tidal CO₂ pressure (PET_CO2) did not change during the experimental protocol. Pa_CO2  PET_CO2 remained steady before CO₂ insufflation in the different positions and when CO₂ was insufflated in the horizontal position. However, the combination of head-up 20° tilt and CO₂ insufflation increased Pa_CO2  PET_CO2. As a consequence of intraperitoneal CO₂ insufflation, CO₂ significantly increased.

Hemodynamic variables. Before CO₂ insufflation, the preparation remained steady because hemodynamic variables were similar in the three control horizontal positions, H1, H2, and H3 (Table 2). After a 20° head-down tilt, MAP, CVP, and MPAP increased, whereas heart rate and PCWP did not change. PVP increased, but HVP did not. Cardiac output and HABF did not change, but PVBF significantly increased (+16%). In the 20° head-up tilt, MAP, MPAP, CVP, PCWP, PVP, and HVP decreased significantly as well as cardiac output (14%), HABF (19%), and PVBF (13%). Thus head-down tilt increased THBF, whereas head-up tilt decreased it. The 10° head-up and head-down tilts induced minor modifications.

View larger version (25K): [in this window] [in a new window]   Fig. 1.   Changes (%) of cardiac output, hepatic artery blood flow, and portal vein blood flow during changes of tilt in absence (A) and in presence (B) of pneumoperitoneum. 0°, Horizontal position; 20° and 10°, head-down tilts; 10° and 20°, head-up tilts. A: baseline value is value obtained before changes of tilt. B: to assess effect of CO2 insufflation ± changes of tilts, baseline value was obtained before CO2 insufflation (H3). During pneumoperitoneum, intra-abdominal pressure ranged from 14.5 to 16.8 mmHg.

Variables of oxygenation. Variables of oxygenation are given in Table 4. Systemic DO₂ and O₂ significantly changed during the protocol (P < 0.001), but no difference was observed when the effects of tilt and CO₂ insufflation were compared. Similar results were found for the hepatic variables of oxygenation. Moreover, CO₂ insufflation and position had no effect on lactate uptake through the liver, and no switch from lactate uptake to lactate release was observed.

	DISCUSSION

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This study clearly shows that THBF increases when anesthetized pigs are positioned in the head-down tilt but decreases when they are in the head-up tilt. CO₂ insufflation increases HABF with no effect on THBF. The combination of CO₂ insufflation and head-down tilt has a beneficial effect on hepatic perfusion, whereas when the pneumoperitoneum is associated with the head-up tilt THBF is not modified. Consequently, the combination of CO₂ insufflation and changes in position do not compromise hepatic blood flow in our model, suggesting that hepatic blood flow may be preserved during laparoscopy if tilt does not exceed 20° and if the IAP increase induced by CO₂ insufflation remains <15 mmHg.

Controversial results have been published about the modification of hepatic and mesenteric blood flows during elevated IAP. In early studies, IAP was increased by infusing balanced salt solutions (4, 5) or by inflating bags (3, 21) in the abdomen to mimic the increased IAP observed in massive ascites, bowel distension, abdominal bleeding, or omphalocele in newborns. Two recent studies used a pneumoperitoneum to increase IAP, but the gas insufflated was either CO₂ (11) or helium (2). In anesthetized pigs, Diebel et al. (5) showed that the IAP increase (induced by fluid infusion in the abdomen) may cause significant impairment of hepatic perfusion. Despite normal MAP and cardiac output, PVBF and HABF fell to 65 and 45%, respectively, of the baseline value at an IAP of 20 mmHg. When IAP reached 40 mmHg, cardiac output also decreased and hepatic hypoperfusion worsened. Mesenteric blood flow also decreased when IAP reached 20 mmHg (2-4). In contrast, in anesthetized dogs, increasing IAP up to 20 mmHg did not compromise mesenteric perfusion (16). When intraperitoneal pressure was increased up to 25 mmHg by inflating a large bag into the peritoneum, HABF increased and PVBF decreased but the increase in HABF was not sufficient to maintain THBF (21). Finally, when IAP was increased by CO₂ insufflation in anesthetized dogs, PVBF decreased but HABF was maintained (11). The various types of animals used for the studies (dogs, neonatal lambs, and pigs) may explain these conflicting results. Moreover, anesthesia was maintained by either pentobarbital (2, 11, 21) or isoflurane (5). The volemic status of the animals also interferes in the relationship between hemodynamic variables and IAP. Increasing IAP to 40 mmHg decreases cardiac output by 53% in hypovolemic dogs and by 17% in normovolemic dogs but raises cardiac output by 50% in hypervolemic dogs (14). Consequently, cardiac output at an IAP of 15 mmHg remained steady (5) or decreased (2, 3, 11, 21), whereas in anesthetized pigs cardiac output was slightly increased when IAP was moderately increased (9, 18, 23). Thus in normovolemic animals, when IAP remains below 20 mmHg, systemic and hepatosplanchnic perfusion or hemodynamics are not compromised. Because in clinical studies the IAP increase remains <15 mmHg (12, 13, 25, 27), we chose to maintain this amplitude of IAP 15 mmHg during CO₂ insufflation.

In our study, after CO₂ insufflation, cardiac output and PVBF did not change significantly but HABF increased (+49%). However, the HABF increase was insufficient to concomitantly increase THBF. Because we used CO₂ insufflation to produce the pneumoperitoneum, we increased both IAP and CO₂ content in the abdomen. Besides the fact that increased IAP may modify regional blood flows, low pH and high PCO₂ in the portal vein may increase HABF and decrease PVBF (7). In our study, the greatest changes in pH and PCO₂ in the portal vein were 7.35 ± 0.02 and 53.5 ± 2.1 mmHg, respectively. Because these changes were lower than those necessary to modify hepatic blood flow (7), we postulated that variations of pH and PCO₂ had a minor effect on hepatic flow in our study. Further studies in which helium instead of CO₂ would be used at a similar IAP level might confirm this assumption. Because we continuously infused pigs with fluid during the protocol (8 ml · kg¹ · h¹), we speculated that our pigs were normovolemic. The slight increase in cardiac output (+17%) observed during CO₂ insufflation is unlikely to be the consequence of hypercapnia because we maintained a normal Pa_CO2. Direct stimulation of intra-abdominal receptors induced by intraperitoneal distension or increased abdominal CO₂ concentration may cause this cardiac output increase (20). Moreover, blood volume is limited in pig lower extremities and a large blood volume is unlikely to be sequestered in the lower part of the body during CO₂ insufflation. In human studies, cardiac output is either unchanged (25, 26), increased (15), or decreased (8, 12, 13) during pneumoperitoneum. Besides the volemic status and levels of IAP, rates of CO₂ insufflation and time intervals between insufflation and data collection may explain the various evolution of cardiac output in human studies.

Besides the pneumoperitoneum, changes in position facilitate access to organs in the upper or lower part of the abdomen during laparoscopy. Before CO₂ insufflation, when pigs were positioned in the head-down tilt PVBF increased, but when they were in the head-up tilt both hepatic flows decreased. The changes in THBF followed the changes in cardiac output. The combination of CO₂ insufflation and changes in position, as observed in clinical practice, had a beneficial effect on hepatic perfusion in the head-down tilt, whereas THBF was similar in the horizontal position without pneumoperitoneum and in the head-up tilt during CO₂ insufflation. In anesthetized patients, progressive increases in IAP to 20 cmH₂O increased cardiac output in both horizontal and head-down tilts (15). This result was not confirmed in healthy women who underwent laparoscopic hysterectomy in which the combination of anesthesia, head-down tilt, and pneumoperitoneum decreased cardiac output (8). In awake volunteers, the head-down tilt increased the cardiopulmonary blood volume with a concomitant cardiac output increase (19). Joris et al. (13) showed that the combination of anesthesia, head-up tilt, and pneumoperitoneum produced a 50% decrease in cardiac output in healthy patients during laparoscopic cholecystectomy. No information is available on the modifications of hepatic blood flow during clinical laparoscopy. Our results suggest that the combination of CO₂ insufflation and changes of position in normovolemic patients does not compromise hepatic blood flow.

Besides the changes in position and the increased IAP, other parameters may also interfere with the hepatic circulation during laparoscopy, such as the type of anesthesia and the minute ventilation. Pancuronium and fentanyl (6) do not significantly affect the hepatic blood flow. Because the effect of pentobarbital remains more controversial (6), anesthetic drugs were continuously infused to avoid major effects of anesthesia on hepatic perfusion. We must also consider that THBF has been altered by increasing the tidal volume to maintain Pa_CO2 constant, through an increase in intrathoracic pressures after the increase in intra-abdominal pressures (22, 24). CO₂ insufflation also increased HVP, PVP, and the difference PVP  HVP, and these modifications of pressure around the liver might transfer blood volume from the hepatosplanchnic region to the chest and increase cardiac output (1, 30).

CO₂ immediately increases after CO₂ insufflation and remains steadily elevated during the pneumoperitoneum, as previously described in a similar animal model (9). The fact that CO₂ does not increase with nitrogen (10) or helium (17) insufflation demonstrates that CO₂ absorption from the abdominal cavity largely contributes to this increased CO₂. Changes in metabolic activity are not involved, because O₂ did not change as already shown (9). Moreover, no evidence of hypoxia might explain the elevated CO₂, because systemic and hepatic variables of oxygenation remained unchanged during the study.

In summary, the combination of CO₂ insufflation and changes in position did not compromise hepatic blood flow in our model of anesthetized pigs, suggesting that hepatic blood flow may be preserved during laparoscopy if tilt does not exceed 20° and if the IAP increase following CO₂ insufflation remains <15 mmHg. This study also points out all the parameters that interfere with the hepatic perfusion. Increased ventilation to maintain a normal Pa_CO2, head-up tilt, anesthetic drugs, and high PCO₂ in the portal vein may decrease hepatic perfusion, whereas head-down tilt and CO₂ insufflation have positive effects. All these parameters, including the volemic status of the patients, must be taken into consideration when performing surgical laparoscopy in patients suffering from patent or unknown diseases.