Subclinical hepatic dysfunction in laparoscopic cholecystectomy and laparoscopic colectomy

Y. Kotake1, J. Takeda1, M. Matsumoto1, M. Tagawa1 and H. Kikuchi3

1Department of Anesthesiology and 3Department of Laboratory Medicine, Keio University, Shinjuku, Tokyo, Japan*Corresponding author: Department of Anesthesiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

Accepted for publication: July 12, 2001


    Abstract
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 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Laparoscopic surgery causes a reduction in hepatic blood flow due to a number of factors, including raised intra-abdominal pressure, the neurohumoral response to surgical stress and the effect of patient position. The clinical significance of the phenomenon is not fully understood. Plasma concentrations of alcohol dehydrogenase (AD) and glutathione S-transferase (GST), which are concentrated in the centrilobular acinus of the liver, sensitively reflect hepatic hypoperfusion, and can be used to monitor reductions in hepatic blood flow. We compared perioperative AD, GST, aspartate aminotransferase (AST, normal range 14–32 IU litre–1) and alanine aminotransferase (ALT, normal range 8–41 U litre–1) concentrations in patients undergoing laparoscopic cholecystectomy or laparoscopic colectomy to study how patient position and surgical manipulation of the liver affect hepatocellular integrity during laparoscopy. There were significant postoperative increases in AD and GST in the cholecystectomy group [mean (SD) peak concentration 10.8 (4.7) U litre–1 and 113 (55) µg litre–1 respectively]. Although the duration of pneumoperitoneum was longer in the colectomy group, there were no comparable perioperative increases in AD and GST in this group [peak concentration 4.0 (4.0) U litre–1 and 33 (35) µg litre–1 respectively]. AST and ALT on the first postoperative day were significantly higher in the laparoscopic cholecystectomy group (41 and 34 U litre1 respectively) than in the laparoscopic colectomy group (24 and 18 U litre1; P<0.05 for each). These results indicate that patient position and the effects of surgical manipulation of the liver affect perioperative hepatic perfusion significantly.

Br J Anaesth 2001; 87: 774–6

Keywords: enzymes, alcohol dehydrogenase; enzymes, glutathione S-transferase; surgery, laparoscopy; surgery, cholecystectomy; surgery, colectomy


    Introduction
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Laparoscopic cholecystectomy using carbon dioxide insufflation induces intraoperative cardiovascular changes. These are due to a number of factors, including the reverse Trendelenburg position; increased intra-abdominal pressure; the neurohumoral response to surgical stress; and the effects of carbon dioxide absorption.1 A previous study has shown that laparoscopic cholecystectomy cause transient hepatic hypoperfusion.2 However, the clinical significance of this change remains unclear and detailed studies are warranted.3

Hepatic alcohol dehydrogenase (AD)4 and glutathione S-transferase (GST)5 are concentrated in centrilobular hepatocytes and are sensitive enzymes of hepatocellular damage. Thus, perioperative AD and GST levels should clarify the clinical significance of the reduced hepatic blood flow associated with laparoscopic procedures. Changes in splanchnic blood flow have also been linked to the effects of patient position in laparoscopic surgery.6 A comparison of laparoscopic cholecystectomy and laparoscopic colectomy, which are performed using different patient positions and at different surgical sites, may reveal the effects of positioning and surgical manipulation on hepatic perfusion.

In this study we compared perioperative plasma concentrations of AD and GST in these two groups of patients to evaluate the effects of laparoscopic surgery on hepatocellular integrity. Perioperative changes in serum transaminase concentrations were also monitored.


    Methods and results
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
With approval from the institutional Ethics Committee and informed consent, 14 patients undergoing either laparoscopic cholecystectomy (n=7) or laparoscopic colectomy (n=7) were studied. All patients were premedicated with oral diazepam 5 mg and i.m. atropine 0.5 mg. Anaesthesia was induced with thiopental 4–5 mg kg–1 and vecuronium 0.1 mg kg–1, and was maintained using sevoflurane 2–3%, nitrous oxide 66% and oxygen, with intermittent fentanyl and vecuronium. Patients were ventilated mechanically, and PaCO2 was maintained between 4.0 and 4.7 kPa.

Carbon dioxide insufflation was performed to facilitate laparoscopy, and intra-abdominal pressure was maintained between 1.1 and 1.6 kPa. Patients in the laparoscopic cholecystectomy group were positioned in the reverse Trendelenburg position, while those in the laparoscopic colectomy group were positioned in the Trendelenburg position. Arterial blood was sampled after the induction of anaesthesia, at the end of surgery and 1, 3 and 6 h after surgery for the estimation of plasma AD, GST, aspartate aminotransferase (AST, normal range 14–32 U litre–1) and alanine aminotransferase (ALT, normal range 8–41 U litre–1) concentrations.

Plasma AD concentrations were measured using the method described by Kato and colleagues.7 GST concentrations were measured using the Hepkit enzyme immunoassay (Biotrin, Dublin, Irish Republic). AST and ALT concentrations were measured with a Hitachi 7600 automatic analyser (Hitachi, Tokyo, Japan).

Data are expressed as mean (SD). Statistical analysis was performed using the unpaired t-test and analysis of variance. P<0.05 was considered clinically significant.

There were no significant differences in sex, age [59 (10) vs 67 (8) yr), weight [58 (13) vs 57 (14) kg] or height [158 (8) vs 162 (11) cm] between the laparoscopic cholecystectomy and laparoscopic colectomy groups. The durations of surgery and pneumoperitoneum were shorter in the laparoscopic cholecystectomy group than in the laparoscopic colectomy group [surgery, 62 (32) vs 225 (66) min; pneumoperitoneum, 39 (20) vs 125 (59) min]. The total dose of fentanyl in the two groups was 57 (79) and 100 (58) µg respectively and that of vecuronium 7.7 (1.9) and 14.8 (4.9) mg.

The AD concentration in the laparoscopic cholecystectomy group was significantly elevated by the end of surgery and remained significantly elevated for 3 h after surgery (Table 1). There were no significant increases in AD in the laparoscopic colectomy group. AD concentrations at the end of the procedure and 1 h after surgery were higher in the laparoscopic cholecystectomy group than in the laparoscopic colectomy group.


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Table 1 Perioperative plasma AD, GST and transaminase concentrations in patients undergoing laparoscopic cholecystectomy (Chole) and laparoscopic colectomy (Colon) (n=7 for each group). Data are expressed as mean (SD). n/a = not available. *P<0.05 vs laparoscopic colectomy; {dagger}P<0.05 vs after induction in each subgroup
 
The GST concentration in the laparoscopic cholecystectomy group was significantly elevated at the end of the procedure and 1 h after surgery, but decreased rapidly and had returned almost to the preoperative value 3 h after surgery. As with AD, there were no significant postoperative increases in GST concentration in the laparoscopic colectomy group. The GST concentration in the laparoscopic cholecystectomy group was higher at the end of the procedure and 1 h after surgery than in the laparoscopic colectomy group. The AST concentration in the laparoscopic cholecystectomy group was significantly elevated on the first day after surgery. The mean value was significantly higher in the laparoscopic cholecystectomy group than in the laparoscopic colectomy group 6 h after surgery and on the first day after surgery. The ALT concentration was significantly elevated on the first day after surgery in both groups. It was higher in the laparoscopic cholecystectomy group than in the laparoscopic colectomy group at all time-points.


    Comment
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 Abstract
 Introduction
 Methods and results
 Comment
 References
 
We observed transient perioperative increases in AD and GST in the patients undergoing laparoscopic cholecystectomy, but no such increases were observed in the laparoscopic colectomy group. In both groups, AD and GST returned rapidly to near-preoperative concentrations after surgery, and none of the patients presented with clinical hepatic dysfunction after surgery.

Hepatic hypoperfusion during laparoscopic cholecystectomy has been reported previously.2 3 This finding was attributed to the combined effects of elevated intra-abdominal pressure, hypercapnia and the position of the patient. Humoral factors, such as vasopressin released from the pituitary, may also be involved in changes in hepatic blood flow during laparoscopic surgery.8 Comparison of laparoscopic cholecystectomy and colectomy by the use of a sensitive marker of hepatic dysfunction, such as AD and GST,5 may clarify which factors account for this change, as these two procedures involve different patient positions and types of surgical manipulation.

Although the normal ranges of AD and GST concentrations have not been clearly defined, the preoperative upper concentration limits of these enzymes have been reported as 5 U litre–1 and 10 µg litre–1 respectively. The increases in AD and GST observed in this study indicate that laparoscopic procedures are associated with disturbances in hepatocyte integrity. As much smaller fluctuations in GST were observed during mastectomy under sevoflurane anaesthesia,9 these changes can be attributed to the laparoscopic procedure. Patients in the laparoscopic cholecystectomy group showed significantly greater postoperative increases in plasma AD and GST than those in the laparoscopic colectomy group. Although the duration of pneumoperitoneum was longer in patients undergoing laparoscopic colectomy than in the laparoscopic cholecystectomy group, perioperative AD and GST concentrations were not correlated with the duration of pneumoperitoneum in either group. Despite the small sample size, these findings support the theory that factors other than elevated intra-abdominal pressure have a significant effect on hepatic perfusion during laparoscopic surgery.

One possible factor is the effect of patient position on blood flow. Sato and colleagues used transoesophageal echocardiography to monitor hepatic blood flow during laparoscopic cholecystectomy and concluded that the combination of pneumoperitoneum and head-up positioning resulted in decreased hepatic perfusion.3 Junghans and colleagues also found that the combination of the head-up position with a higher intra-abdominal pressure resulted in the greatest disturbance in hepatic perfusion.10

The effects of surgical manipulation of the liver and the neurohumorally mediated response to surgical stress may also contribute to the transient disturbance of hepatocyte integrity. As direct compression of the liver is not severe in laparoscopic cholecystectomy, it is probable that neurochemical factors such as vasopressin and norepinephrine play a more significant role in causing the transient reduction in hepatic blood flow. Additionally, application of diathermy to the liver surface might contribute to the elevated AD, GST and transaminase concentrations after laparoscopic cholecystectomy. However, the effect of diathermy should be immediate and zone-independent, and AD, GST and the transaminases should therefore increase simultaneously. As this was not the case, we believe that the observed change was caused by a disturbance of intraoperative hepatic perfusion.

Our findings show that the changes in the plasma concentrations of these enzymes follow somewhat different time-courses. We assume that the changes in AD and GST reflect an identical reduction in hepatic blood flow, and that the differences in the time-courses are attributable to the different plasma half-lives of the two enzymes. It has not yet been determined whether AD or GST provides the more accurate indicator of hepatic hypoperfusion.

In conclusion, we found that patients undergoing laparoscopic cholecystectomy showed signs of subclinical hepatocellular injury attributable to hepatic hypoperfusion. The finding that there were significantly higher perioperative increases in plasma AD and GST in patients undergoing laparoscopic cholecystectomy than those undergoing laparoscopic colectomy suggests that the increased intra-abdominal pressure caused by carbon dioxide insufflation was not the sole cause of the hepatocellular injury. The head-up positioning of the patient, the effects of direct manipulation of the liver and the neurohumoral response to upper abdominal surgical stress may all play important roles in the disturbance of hepatic perfusion during laparoscopic cholecystectomy. Further study of these individual factors is warranted.


    References
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
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