38. Liver Function and Portal Blood Flow

38. Liver Function and Portal Blood Flow

Michael W. Potter, M.D.

Shimul A. Shah, M.D.

Mark P. Callery, M.D., F.A.C.S.

The effect of CO

pneumoperitoneum on hepatic function is clinically insignificant in most patients. Given the number of laparoscopic procedures performed each day, this is fortunate. Theoretically, some patients, such as those with diminished hepatic reserve, may require an alternative to pneumoperi- toneum to recover most effectively from surgery.

A. Liver Physiology

The liver is the largest organ in the peritoneal cavity, weighing between 1200 and 1600 g in the average adult. Blood supply to the liver is from both the portal vein (70%) and hepatic artery (30%). The portal vein is a low-pressure, thin- walled vessel, receiving almost all the venous drainage from the digestive tract between proximal stomach and upper rectum, as well as the spleen and pancreas.

Drainage of blood from the liver occurs through the hepatic veins, which drain directly into the inferior vena cava.

The liver has a broad range of functions, which reflect its key location inter-

posed between the abdominal viscera and the systemic circulation. It is essen-

tial for maintenance of energy homeostasis in the body. It is the first organ to be

exposed to pancreatic endocrine secretions, and its sensitivity to these polypep-

tides can determine the overall catabolic or anabolic balance in the body. A large

number of proteins including plasma proteins, acute-phase proteins, and coagu-

lation factors are synthesized by the liver. The liver is also responsible for the

detoxification and secretion of various substances, including exogenous sub-

stances such as drugs and endogenous substances such as heme. Finally, the

liver’s reticuloendothelial cell system provides surveillance of the bloodstream

and produces cytokines important to the systemic immune response [1]. There-

fore, any insult to such a complex organ could affect the overall well-being of

the patient and induce morbidity.

B. Pneumoperitoneum

Carbon dioxide pneumoperitoneum is the usual method for achieving laparo- scopic access. It is achieved by insufflation of the abdominal cavity to a pres- sure in the range of 10–15 mmHg. CO

is preferred because it is abundant, inexpensive, rapidly absorbed, and does not support combustion. This latter quality is also a drawback because it becomes biologically active when dissolved in the blood and can affect acid-base status and other physiologic functions.

Other gases have been investigated as alternatives to CO

including room air, oxygen, nitrous oxide, nitrogen, helium, and argon, which prevent the hemody- namic changes associated with CO

absorption but still result in elevated intraab- dominal pressure. Abdominal wall lifting devices may enable the surgeon to minimize hemodynamic changes altogether, although at this point the visual- ization provided by these lift devices is substandard.

C. The Effect of Pneumoperitoneum on Hepatic Function

Insufflation of the abdomen applies a direct pressure to the liver parenchyma because it is a solid organ and is not easily compressed. The actual total pres- sure exerted on the liver may be higher than the insufflation pressure because its location just beneath the right hemidiaphragm subjects the liver to pressures from above during positive-pressure ventilation. This mechanical pressure alone may be enough to produce some damage to the liver. The serum markers com- monly known as “liver function tests” are good indicators of damage to hepato- cytes. Routine laparoscopic cholecystectomy (LC), in patients who had neither preoperative hepatic dysfunction nor intraoperative bile duct injury, causes sig- nificant increases in aspartate aminotransferase (AST) and alanine aminotrans- ferase (ALT). In one study, AST was increased in 79% of patients and ALT in 82%. Levels were as high as 1.8 and 2.2 times the mean preoperative levels, respectively, returning to normal within 72 hours. Alkaline phosphatase (ALP) and total bilirubin were elevated in 53% and 12% of patients, respectively, although the differences when compared to preoperative levels were not statis- tically significant [2]. Elevation of these liver enzymes is not specific for damage caused by pneumoperitoneum alone, because use of the electrocautery, tension on the liver due to gallbladder retraction, transient elevation of biliary pressures as a result of kinking of the extrahepatic biliary tree, and other sorts of minor liver trauma that occur during surgery may contribute.

Some evidence implicating pneumoperitoneum-related increased intraab-

dominal pressure as a cause of liver enzyme elevation was provided by Morino

et al., who examined 32 patients randomly assigned to undergo LC under insuf-

flation pressures of 10 or 14 mmHg. All patients developed an increase in AST,

ALT, bilirubin, and prothrombin time postoperatively, although only the levels

of AST and ALT attained statistical significance. There were differences between

the two intraabdominal pressure groups; the higher enzyme levels were noted in

the 14 mmHg group. Additionally, the liver function of a group of 20 laparo- scopic cases insufflated to 14 mmHg that did not involve the liver was compared to the results of the cholecystectomy patients. In this group, AST and ALT were found to be elevated to levels higher than in the 10 mmHg LC group but not as high as the 14 mmHg LC group [3]. In a different study that compared patients receiving LC to those undergoing open cholecystectomy (OC), a significant increase in AST and ALT was found only in the laparoscopic group [4]. These data suggest that the hepatic damage is related to the CO

pneumoperitoneum, perhaps due to compression of the relatively low pressure portal venous system.

This damage does not manifest itself as clinically notable liver dysfunction, as there was no morbidity attributable to the liver reported in these studies. The markers more specific for true liver function (total bilirubin, prothrombin time) rather than liver damage were also not significantly increased in these studies.

D. The Effect of Pneumoperitoneum on Hepatic Blood Flow

The effects of increased intraabdominal pressure on blood flow in general have been well characterized and include increases in mean arterial blood pres- sure and systemic vascular resistance. Splanchnic blood flow is affected by pneu- moperitoneum as well. In dogs subjected to an elevated intraperitoneal pressure, blood flow to the liver, spleen, and intestines decreases, likely due to compres- sion of the portal vein [5, 6]. In pigs, portal venous flow is decreased by two- thirds with higher levels of intraabdominal pressure [7]. In humans undergoing LC, portal blood flow, as measured by duplex doppler ultrasound, decreased by 53% during insufflation of the abdomen to 14 mmHg [8]. Whether pneumoperi- toneum causes compression of the hepatic artery and decrease in arterial blood flow is controversial. Most studies have found that there is little change with increased intraabdominal pressure (IAP); however, Klopfenstein et al. found a 49% increase in hepatic arterial flow using transit-time ultrasound [9].

This overall decreased blood flow correlates with liver dysfunction. Hepatic clearance of indocyanine green (ICG) is impaired in pigs undergoing laparoscopic surgery or simple CO

pneumoperitoneum as compared to animals undergoing open surgery [10]. This diminished blood flow could conceivably contribute to alterations in the ability of the liver to process various anesthetic agents, as it does ICG. Additionally, CO

insufflation of the rat abdomen leads to decreased particle elimination by the liver mononuclear phagocyte system as compared to open surgery or endoscopic surgery without pneumoperitoneum [11].

E. The Effect of CO 2 on the Liver

Changes in hepatic blood flow may not be caused entirely by the effects of

the pressure of the pneumoperitoneum on the portal vein and inferior vena cava

(IVC). Local microcirculatory changes may occur as a result of increased PCO

caused by CO

pneumoperitoneum, and this could be a mechanism for hepatic dysfunction; however, this does not seem to be a predominant factor. In a study of dogs insufflated to 14 mmHg with CO

or helium (He), all hemodynamic mea- surements that were made were equivalent between the two groups, except that the PCO

measured at the IVC was higher in the CO

group [5]. On the other hand, a similar study showed that helium was associated with a greater decrease in hepatic blood flow than CO

pneumoperitoneum [12].

There is some concern regarding the use of CO

in laparoscopic liver resec- tion. Because of pressure differences between the hepatic venous system, which normally has a pressure of 5–10 mmHg, and the elevated intraabdominal pres- sure due to the pneumoperitoneum (10–14 mmHg), there is the potential for gas embolism when the hepatic venous system is injured and thus directly exposed to the pneumoperitoneum. During laparoscopic liver resection, CO

microbub- bles seem to form in the hepatic circulation [13]; these microbubbles could con- ceivably travel to the vena cava and right atrium, creating a gas lock. The benefit of using a physiologic gas such as CO

rather than an inert gas like helium might come in to play in this situation because CO

can be rapidly dissolved and absorbed in the blood, producing only transient and minor symptoms [14].

Abdominal wall lift devices have been employed due to concern for CO

embolism [15, 16], but laparoscopic hepatic resection under pneumoperitoneum has been well described without significant changes [14, 17].

F. Special Considerations

As is clear from the preceding studies, the liver is affected by pneumoperi- toneum, but not usually to a clinically evident level. Are there cases in which this liver dysfunction can become clinically important? The most obvious situ- ation in which this might occur is in patients who have preexisting limitations of hepatic reserve. Cirrhotic livers or those with chronic hepatitis may not have the functional capacity to recover from the insult that pneumoperitoneum incurs.

One study addresses this question by evaluating the liver’s ability to convert amino nitrogen in the blood to urea nitrogen in patients with cirrhosis as a measure of the metabolic stress response. There was no significant difference, in this value, between the metabolic stress response of those patients who under- went OC and those who had a laparoscopic procedure [18]. In these patients with limited reserve, it may be that any impairment of hepatic function that may be induced by CO

pneumoperitoneum is well compensated for by the decreased need for a metabolic stress response afforded by minimally invasive surgery.

Another area in which pneumoperitoneum might affect the liver is laparo-

scopic cancer surgery. Decreasing morbidity, patient comfort, and hospital stay

would be a boon to patients requiring cancer resection. There is some concern,

however, that the presence of pneumoperitoneum may increase the chances for

tumor dissemination and metastases. Tumor cells that are shed hematogeneously

during resection are likely to find their way into the portal vein. In a study of

tumor cells injected directly into the portal veins of rabbits, Ishida et al. found

a significant increase in the subsequent amount of tumor found in the livers of

those animals that were exposed to pneumoperitoneum when compared to the results in animals that underwent laparotomy [19]. In a similar model, although in mice, Chen et al. found that the number of tumor cells initially localized to the liver was higher in the pneumoperitoneum group, although this increase less- ened over time [20]. These authors propose that impaired hepatic blood flow may create an environment more conducive to tumor cell implantation, that oxygen- derived free radicals created following restoration of blood flow might induce endothelial cell damage and thus allow better tumor cell localization, or that hypercapnia might induce the growth of tumor cells directly. Impaired reticu- loendothelial cell function may also play a role during or following pneu- moperitoneum. These hypotheses have not been adequately investigated in human subjects.

G. Conclusion

Clearly, pneumoperitoneum, whether with CO

or other gases, causes some hepatic damage although effects on hepatic function are limited. Blood flow to the liver is altered, and this affects hepatic clearance of some drugs. These changes are small and clinically insignificant in most situations. As our reper- toire of laparoscopic procedures increases, it will be necessary to consider in what ways pneumoperitoneum can have an effect on the liver and whether alternatives to insufflation would be appropriate. New technologies such as abdominal lift devices with minimal insufflation could minimize any hepatic damage and help to placate worries about impaired hepatic reserve or metastases to the liver.

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