Since the initiation of laparoscopic hepatectomy in 2008, we have standardized a technique for anatomical hepatectomy in which the Glissonean branches and hepatic veins are exposed on the dissecting plane and have also achieved good results.1–5 The maintenance of a dry operative field is important to perform this procedure safely and appropriately. To maintain a dry operative field, intermittent hepatic vascular inflow occlusion is employed to control hepatic inflow, whereas the maintenance of a relatively low central venous pressure (CVP) is used to control backflow bleeding from the hepatic vein, regardless of an open or laparoscopic approach.6–8 An increase in pneumoperitoneum pressure (PPP) has also been reported to control backflow bleeding from the hepatic vein in pure laparoscopic hepatectomy. Although this measure is based on extremely high absorbability of carbon dioxide gas, the risk of pulmonary gas embolism is still of concern.9–12 Although we previously employed increases in PPP to control bleeding from the hepatic vein, we noted that reductions in airway pressure (AWP), which represents a less invasive measure, also effectively reduced bleeding from the hepatic vein.2 Therefore, we conducted this experimental study to clarify the mutual relationship among AWP, PPP, and CVP during pure laparoscopic hepatectomy and to explain clearly the rationale for optimal settings of these pressures to control bleeding from the hepatic vein safely by eliminating the risk of pulmonary gas embolism.
The current study was approved by the Institutional Review Board of Tokyo Metropolitan Cancer and Infectious disease Center Komagome Hospital, and all animals were managed according to the ethical rules for animal studies.
Six male piglets (mean age of 13 weeks and mean weight of 39 kg) underwent experiments under general anesthesia in a supine position. They were deprived of food overnight before the experiments, but had free access to water. General anesthesia was induced and maintained with oxygen and sevoflurane. After intubation, the right external jugular vein was cannulated with a 16-gauge catheter and the tip of the cannula was placed in the right atrium to measure CVP. CVP was adjusted to 10 ± 2 mmHg under AWP of 0 cmH2O by adjusting the infusion rate at the beginning of each experiment. Arterial blood pressure and heart rate were measured at the superficial cutaneous artery of the ear, which had been cannulated in advance. A 12-mm trocar was placed next to the urethral orifice and pneumoperitoneum was established using carbon dioxide gas.
The fundamental procedure of the experiment was to measure CVP at 9 different levels of AWP. Under each fixed level of PPP, AWP was elevated in increments of 5 cmH2O from 0 to 40 cmH2O (9 levels). At each level, the AWP was maintained for approximately 10 seconds by the inspiratory-hold maneuver and plateaued CVP was recorded. After measurements had been taken at an AWP of 40 cmH2O (the highest level), AWP was decreased by opening the ventilation circuit. Mechanical ventilation was then resumed at 10 mL per 1 kg for tidal volume at a respiratory rate of 14 breaths per minute and was continued until circulation was stabilized in the piglet. This 1 cycle of measurement under a fixed level of PPP was repeated 3 times (Fig. 1). These 3 measurement cycles were then repeated with decreases in PPP at decrements of 5 mmHg from 25 to 0 mmHg. Piglets subsequently underwent laparotomy and 3 measurement cycles were performed under atmospheric pressure. Data from a total of 18 measurements of CVP (3 cycles for each of the 6 piglets) were collected at each level of AWP under each level of PPP. However, measurements were discontinued when systolic blood pressure fell below 60 mmHg, mechanical ventilation was resumed, and this was defined as a missing value.
The measurements of this study were performed on the premise that the pressure levels in the atrium and inferior vena cava (IVC) are almost the same or at least change in parallel to each other, on the basis of previous reports.13
Multiple regression analysis was performed among AWP, PPP, and CVP. Correlation and regression analyses were performed between PPP and CVP and between AWP and CVP. All P values less than 0.05 were considered significant. Statistical analyses were performed with SPSS 11.0 J for Windows.
Eighteen measurements of CVP were obtained at an AWP level of less than 35 cmH2O; however, missing values appeared at frequencies of 79% and 84% at AWP levels of 35 and 40 cmH2O, respectively.
The result of the multiple regression analysis among CVP, AWP, and PPP was CVP (mmHg) = 0.308 × AWP (cmH2O) + 0.229 × PPP (mmHg) + 10.890 (R = 0.891, P < 0.001), which confirmed that AWP and PPP both correlated with CVP. AWP had a stronger correlation than PPP (standardized partial regression coefficients: AWP: 0.765, PPP: 0.450, P < 0.001).
A positive correlation was observed between PPP and CVP when AWP was 5 cmH2O or higher (P < 0.001), and the correlation coefficient became higher with increases in the AWP (Fig. 2). Under high AWP (from 25 to 40 mmHg), CVP was persistently higher than PPP as a result of reactive increases in CVP due to elevations in PPP. Under low AWP levels (from 0 to 20 mmHg), CVP did not increase or often decreased, especially when PPP was higher than CVP (Fig. 2).
A positive correlation was noted between AWP and CVP under each of the 7 levels of PPP (P < 0.001), and the correlation coefficient became higher with increases in PPP (Fig. 3).
Bleeding from and pneumoperitoneum gas influx into the IVC or hepatic vein during laparoscopic hepatectomy depend on the pressure gradient between PPP and CVP,12,14 and blood loss can be reduced by maintaining low CVP.15–19 Low CVP can be maintained by fluid restriction, diuretics, a converse Trendelenburg position, and/or clamping the IVC below the liver,20–22 along with reductions in AWP, namely, intrathoracic pressure.23–26 However, these are clinical findings that have mainly been obtained during an open approach. Laparoscopic surgery is performed by maintaining intraperitoneal pressure at approximately 10 mmHg, whereas conventional open surgery is performed under atmospheric pressure. The multiple regression analysis in the current study revealed that AWP and PPP both correlated with CVP and not only AWP but also PPP independently affected the level of CVP. However, intraperitoneal pressure, which can be controlled by adjusting the PPP in a sealed abdominal cavity, is known to exert various effects on its surroundings. For example, decreases have been reported in tidal volume following increases in intraperitoneal pressure because the diaphragm bulges outward into the thoracic cavity.27,28 If the anesthesiologist does not notice an increase in PPP, AWP can be increased to secure a sufficient ventilatory volume. The intraperitoneal pressure level also indirectly affects CVP, in addition to direct effects on the hepatic vein and IVC around the liver, which surgeons have a clear view of during laparoscopic hepatectomy. Indirect effects, for example, those via intrathoracic pressure and decreases in venous return from the lower half of the body because of flattening of the IVC by higher PPP, must also be considered.29,30
Results With High AWP
The correlation between PPP and CVP became stronger when AWP was increased under a positive intrathoracic pressure (5 mmHg or more); the rate of increase in CVP as a result of elevations in PPP became higher under higher AWP levels (Fig. 2). Accordingly, CVP was persistently higher than PPP under high AWP levels (from 25 to 40 mmHg), as indicated on the left upper side of the equilibrium line in Figure 2. Assuming that neither bleeding from nor pneumoperitoneum gas influx into the injury hole in the hepatic vein occurs when PPP and CVP are equal (indicated by the equilibrium line in Fig. 2) and that bleeding and gas influx occur on the left and right sides of the equilibrium line, respectively, these results demonstrate that, when AWP is high, increases in PPP do not effectively control backflow bleeding from the hepatic vein. Furthermore, the systolic blood pressure may fall markedly because of decreases in cardiac output when both AWP and PPP are very high, as when missing values were noted in this study. Systemic venous return is regulated by the pressure gradient between the right atrium pressure and peripheral venous pressure.31,32 Therefore, when CVP increases as a result of elevations in both AWP and PPP, systemic venous return decreases with subsequent suppression of cardiac output.33,34 The simultaneous occurrence of this phenomenon with the depletion of blood, that is, massive bleeding, can lead to a detrimental condition caused by a critical decrease of systemic return.
Results With Low AWP
In the absence of intrathoracic pressure (AWP 0 mmHg), no correlation was observed between the PPP and CVP (Fig. 2). That was mainly because the effect of the PPP on the CVP was buffered in the thoracic cavity. Under low AWP (from 0 to 20 mmHg), increases in PPP caused smaller increases in CVP; accordingly, PPP became higher than CVP (Fig. 2). These results suggest that when the AWP is low, increasing the PPP is effective to control bleeding because of backflow from the hepatic vein. In most cases, even if PPP becomes higher than CVP, fortunately, clear clinical problems do not occur because the absorbability of carbon dioxide gas is extremely high. However, our study revealed another point that requires caution when AWP is low.
As indicated on the right lower side of the equilibrium line in Figure 2, when PPP was higher than CVP, CVP did not increase or often decreased with increases in PPP. When PPP becomes higher than CVP, venous return from the lower half of the body decreases because of flattening of the IVC by higher PPP.29,30 Furthermore, elevations in PPP without increases in CVP may have markedly enhanced pneumoperitoneum gas influx into the IVC or hepatic vein. Surgeons should be aware that these results indicate that further increases in PPP beyond the level of CVP under low AWP levels markedly increase the risk of pulmonary gas embolism.
Effects of Cyclical Changes in AWP in Clinical Practice
In the current study, a positive correlation was observed between AWP and CVP under any PPP level, and the correlation coefficient became higher with increases in PPP (Fig. 3). This result suggests that the rate of change in CVP because of changes in AWP is higher when PPP is elevated. In clinical practice, AWP is not fixed during surgery; it increases and decreases in a cyclical manner as a result of positive pressure ventilation. Therefore, the pressure difference in CVP between the peak inspiratory phase (when AWP is the highest) and the end expiratory phase (when AWP is the lowest) may become larger with increases in PPP during surgery. Thus, when the hepatic vein or IVC has been injured, bleeding may increase in the inspiratory phase, during which AWP is higher, and the amount of pneumoperitoneum gas influx in the expiratory phase, during which AWP is lower, may also increase with elevations in PPP. The condition of bleeding or pneumoperitoneum gas influx may change in a cyclical manner under positive pressure ventilation. If PPP is increased rapidly when a surgeon encounters bleeding in the peak inspiratory phase, in which bleeding is controlled well, pulmonary gas embolism may develop because of elevations in the amount of pneumoperitoneum gas influx in the end expiratory phase. Surgeons should at least be aware of this, even if clear clinical problems fortunately do not occur because the absorbability of carbon dioxide gas is extremely high.
Pressure Arrangement in Komagome Hospital
In our hospital, pressure during laparoscopic hepatectomy is adjusted as described below.2 A patient is placed in the converse Trendelenburg position, fluid is restricted as much as possible, and PPP is set at 10 mmHg, whereas AWP is not adjusted at a particularly low level. When the operative field is not dry enough during parenchymal dissection, Pringle's maneuver is initiated6 and, if necessary, AWP is decreased by 5 cmH2O. We rarely or never increase PPP. In the case of strong bleeding from a hole caused by injury of the IVC or hepatic vein, ventilation is stopped temporarily to reduce the intrathoracic pressure to zero, and the site of bleeding is identified and repaired. Regarding operative indications, patients with respiratory issues that may cause insufficient ventilation caused by pneumoperitoneum are excluded from the indication criteria of pure laparoscopic hepatectomy, especially when the IVC or main trunk of the hepatic vein will be exposed.
The results of the current study suggest that bleeding from the hepatic vein cannot be controlled by increasing PPP under high airway pressure, but can be controlled under low AWP; however, the risk of pulmonary gas embolism increases simultaneously under low AWP. Therefore, to control bleeding from the hepatic vein, reducing CVP by lowering AWP is considered safer than increasing PPP.
This study was supported by a grant from the Japanese Foundation for Research and Promotion of Endoscopy. The authors thank Koji Asai, Chie Takishita, Misato Amaki, and Kazuya Takahashi for supporting this study.
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