Evaluation Of Effects Of Laparoscopic Surgery On Hepatic FunctionCorrespondence Address :
Dr.Tauro LF,Dept.of General SurgeryFr. MullerMedicalCollegeHospitalKankanady,Mangaloreâ575002(D.K.)Karnataka,INDIA)Ph.No:Hosp:(0824)2436301,Res:(0824) 2224911,E-Mail:firstname.lastname@example.org
Aim:The purpose of this study was to investigate the effect of laparoscopic surgery on liver function and the possible mechanisms behind such effect.
Methods:Blood samples were collected from 60 patients undergoing various types of laparoscopic procedures, preoperatively once and post operatively on day 1 and day 7. They were tested for liver function by comparing the levels of serum bilirubin, serum alanine amino transferase (ALT), serum aspartate aminotransferase (AST) and serum alkaline phosphatase. The time of CO2 insufflation was also measured.
Results:The levels of serum AST, ALT, bilirubin and alkaline phosphatase increased significantly during the first 48 hrs post operatively. Doubling of pre-op values of AST was seen in 33.3% and of ALT was seen in 31.7%. By 7th post operative day, the levels of AST, ALT, bilirubin and alkaline phosphatase returned to near pre-operative values. CO2 pneumoperitonium was found to be a major cause of increased liver enzymes and serum bilirubin in the study.
Conclusion:Transient elevation of hepatic enzymes occurs after laparoscopic surgery and CO2 pneumoperitoneum seemed to be the major reason.
Laparoscopy, Laparoscopic surgery, Liver enzyme, Pneumoperitoneum
Laparoscopy provides access to the peritoneal cavity for diagnosis and also for many surgical interventions previously only possible by laparotomy. Main advantages of laparoscopic surgery include; reduction of tissue trauma due to small skin incisions and reduction in adhesion formation. The growing interest in laparoscopy is mostly attributable to cumulative evidence suggesting a reduction in patient morbidity, shortening of duration of hospital stay and early return to normal activity.
During the last decade many studies have disclosed âunexplainedâ changes in postoperative liver function tests in patients undergoing laparoscopic procedures. (1), (2) These studies demonstrate that transient elevation of hepatic enzymes could occur after laparoscopic procedures. No causes for this elevation are documented so far. These changes might be attributed to hepatocellular dysfunction secondary to one or combination of CO2 pneumoperitoneum, diathermy extruding liver, branch of the hepatic artery injured and general anesthesia(1). CO2 pneumoperitoneum might be one of the main reasons for the change of serum liver enzymes.
This study was intended to assess the prevalence, and clinical significance of unexplained disturbances in liver enzymes following laparoscopic surgeries.
Aims And Objectives
1. To estimate serum AST, ALT, Serum Bilirubin, and Alkaline Phosphatase in patients undergoing laparoscopic surgeries preoperatively and postoperatively on day 1 and 7.
2. To evaluate the effects of laparoscopic surgery on liver enzymes (AST, ALT, Alkaline Phosphatase) and serum bilirubin.
3. To correlate the duration of laparoscopic surgery with elevation of liver enzymes if any.
This prospective controlled study was conducted to evaluate the effects of laparoscopic procedures on liver function. All the patients studied were selected for laparoscopic procedures after they underwent routine history taking, physical examination and investigations to exclude pre-existing liver diseases or generalized debility.
Patients included in the study were selected by purposive sampling method from those who underwent laparoscopic surgery in the hospital. Investigation review board (Ethical committee) approval was taken prior to the study. The study was conducted over a 2 years period from October 2003 to November 2005. Various laparoscopic procedures were performed in 60 patients and they constituted the study population.
All patients selected for the study had normal values of serum liver enzymes prior to the operations.
The following cases were excluded from the study:
â¢ Cases with coexisting liver disease.
â¢ Cases that developed complications such as bile duct injury, obstruction, infection, leakage and high grade fever during surgery and in the post-operative period.
â¢ Cases who had undergone endoscopic retrograde cholangio pancreatography (ERCP) and endoscopic sphincterotomy within one week before surgery.
In all patients selected for the study, the levels of Aspartate Aminotransferase (AST or SGPT, normal range < 35 U litre-1), Alanine Aminotransferase (ALT or SGOT, normal range < 40 U litre-1), Serum Bilirubin (normal range < 1 mg/dL) and Serum Alkaline Phosphatase (normal range 60-170 U litre-1) were measured pre-operatively (pre-op) once and then post-operatively (post-op) on Day 1 and Day 7.
During surgery, intraabdominal pressure (IAP) was maintained at a range of 12-14 mmHg. CO2 insufflation time was recorded in each procedure. All patients had a nasogastric tube and urinary catheter introduced before surgery. Perioperative antibiotics (ceftriaxone and metronidazole) were administered in all patients.
Serum bilirubin was measured by Identikit using calorimetry. AST and ALT were measured by Raichem spectrophotometer, capable of accurate measurement at 340nm. Serum alkaline phosphatase was measured by Raichem Sphectrophotometer or calorimeter capable of accurately measuring absorbance changes at 405 nm. These patients were followed up at one week, one month, three months and six monthâs intervals following discharge.
All data were expressed as mean +/- standard deviation. Data was analysed for finding the significance of effect of laparoscopy on hepatic function by using students paired t test. P value less than 0.005 was considered to be statistically significant.
Among the 60 patients who constituted the study population, majority were females, i.e. 45 patients (75%) and male patients were 15 (25%). Age distribution of the 60 patients who constituted study population is as below (Table/Fig 1). Majority of these patients were below 50 years of age.
Among the 60 patients constituting the study population, 23 patients underwent appendicectomy and 16 patients underwent cholecystectomy. 15 patients had undergone Laparoscopic Assisted Vaginal Hysterectomy (LAVH) and 3 patients had undergone ovarian cystectomy(Table/Fig 2).
Serum Bilirubin Levels
When compared with pre-op levels, serum bilirubin values increased significantly in post-op day 1 (P =0.001). This value came down to near pre-op levels by post-op day 7 (Table/Fig 3) and (Table/Fig 4). The serum bilirubin level increased significantly within 24-48 hrs following laparoscopic surgery and came down within a weekâs time.
When compared to pre-op levels SGPT values increased significantly in post-op day 1 (P =0.001). This value came down to near pre-op levels by post-op day 7 (Table/Fig 5) and (Table/Fig 6). SGPT levels increased significantly within 24-48 hrs following laparoscopic surgery and came down within a weekâs time.
When compared to pre-op levels SGOT values increased significantly in post-op day1 (P =0.001). This value came down to near pre-op levels by post-op day 7 (Table/Fig 7) and (Table/Fig 8). SGOT levels increased significantly within 24-48 hrs following laparoscopic surgery and came down within a weekâs time.
Alkaline Phosphatase Levels
When compared to pre-op levels, Serum Alkaline phosphatase values increased significantly in post-op day 1 (P =0.001) and came down to near pre-op levels by post-op day 7 (Table/Fig 9) and(Table/Fig 10). Serum Alkaline phosphatase levels increased significantly within 24-48 hrs following laparoscopic surgery and came down within a weekâs time.
In this study it was found that there is a significant co-relation between CO2 insufflation time and cases with elevated liver enzymes level (Table/Fig 10).
Endoscopic surgery is rapidly becoming a popular alternative to traditional operative procedures for a variety of diseases. Many biochemical tests have been used to estimate liver function. In interpreting tests of liver function one must remember that no test is diagnostic of specific liver lesion, and that many tests may be normal even in presence of liver disease and that factors other than liver disease may cause abnormal tests. Carbon dioxide pneumoperitonium induces hemodynamic, pulmonary, renal, splanchnic and endocrinal pathophysiological changes. Splanchnic ischemia is the major pathophysiological change induced by it. Experimental animal studies in rats and pigs have shown decrease in splanchnic macro- and microcirculation depending on the amount of intra-abdominal pressure (3). The immediate consequences of this relative ischemia were an elevation of various hepatic enzymes, including GOT (glutamic oxaloacetic transaminase) and GPT (glutamic pyruvic transaminase), reflecting hepatocytic damage (4), impaired function of the Kupffer cells (5), drop in gastric intramucosal Ph (6), increase in bacterial translocation from the gut, and increased production of oxygen-derived free radicals. A very frequently cited study (7) assessed the splanchnic circulatory changes during high-pressure CO2 pneumoperitoneum. An increase of 5 mmHg, from 10 to 15 mmHg, of the intra-abdominal pressure resulted in blood flow decrease by 40-54% to the stomach, by 32% to the jejunum, by 44% to the colon, by 39% to the liver, and by 60% to the peritoneum. Meanwhile, splanchnic blood flow decreased along with operative time, in spite of a constant intra-arterial pressure (8).
Few studies showed increased levels of aminotransferases(alanine aminotransferase, aspartate aminotransferase) and also of alcohol dehydrogenase and glutathione S-transferase but the phenomenon is transient as these enzymes returned to normal values within 1-3 days(1),(9). These changes are clinically silent in patients with a normal liver function. Transient elevation of hepatic transaminases could occur after laparoscopic procedures. The transient elevation of hepatic transaminases showed no apparent clinical implication in most patients who received laparoscopic surgery according to follow-up observations and feedback from these patients. Nevertheless, these results indicate that, if the patient's preoperative liver function was very poor, laparoscopic surgery might not be the optimal choice for treating certain abdominal diseases (10). An intra-abdominal pressure (IAP) of 12-14 mmHg used in laparoscopic surgery was higher than the normal portal blood pressure of 7-10 mmHg. This operation might therefore, reduce portal blood flow and cause alteration in liver function (11), (12). On the other hand, elevation and depression of IAP in a short time during laparoscopic operation might be causative as well. During laparoscopic procedure, sudden alteration of IAP could cause an undulation of portal blood flow. This undulation and "re-irrigation" of organsâ blood flow may give rise to "ischemia and re-irrigation" damage of tissues and organs, especially Kupffer cells and endothelial cells of hepatic sinusoids (13). The mesothelial cells were found to be bulging up, the intercellular clefts thereby increased in size, and the underlying basal lamina became visible (14). During laparoscopic cholecystectomy (LC), an IAP of 8 mmHg was found to decrease hepatic microcirculation significantly (15). Therefore, elevation of IAP caused by CO2 pneumoperitoneum might be the main reason behind these changes.
A second possible mechanism for alterations of serum liver enzymes after LC is the "squeeze" pressure effect on liver (1). The traction of gallbladder may free these enzymes into blood stream. Third possibility may be local effect of prolonged use of diathermy to liver surface and spread of heat to liver parenchyma. This hypothesis is supported by some other studies (16), (17). But it is not significant here since in our study similar changes are seen in laparoscopic appendicectomies and laparoscopy assisted vaginal hysterectomies too, where liver was not handled at all. In addition, transient liver dysfunction occurs in patients after some general anesthesia (18), (19). This complication is associated with anesthesia-induced changes in splanchnic blood flow and oxygen consumption. But anesthesia could not have acted exclusively to cause these changes, as many studies have shown that there were no such changes in open surgeries with general anesthesia (20).
Another possible mechanism of alterations of serum liver enzymes, which had been considered, was an inadvertent clipping of right branch of hepatic artery or any other aberrant arterial branch supplying blood to liver. When Calot's triangle has dense or cicatricial adhesion, the related arterial branch could be easily injured. This however, should be followed by a massive increase in levels of liver enzymes and usually has clinical implications (21), (22).
Changes in serum liver enzymes in laparoscopic surgery rather than open surgery had been reported before (2), (9). The first factor of consideration here is CO2 pneumoperitoneum (1). All the patients in this study were subjected to CO2 pneumoperitoneum during the surgery and they showed significant changes in post-operative serum liver enzyme levels. This finding is consistent with other similar studies (23), (24), (25). Also it was found in this study that as the time of CO2 pneumoperitoneum increased, elevation in levels of liver enzymes increased. Therefore, elevation of intra-abdominal pressure by CO2 pneumoperitoneum is thought to be the main reason behind these changes. Similar clinical studies in human beings are rare and usually consist of only small groups of patients. A very frequently cited study (7) assessed splanchnic circulatory changes during high pressure CO2 pneumoperitoneum. An increase of 5mmHg from 10mmHg to 15mmHg of intraabdominal pressure resulted in decrease in blood flow by 40-54% to stomach, by 32% to jejunum, by 44% to colon, by 39% to liver and by 60% to peritoneum. Meanwhile, it was also found that splanchnic blood flow decreased along with operative time in spite of a constant intra-arterial pressure.
Also, increased intraabdominal pressure triggers neurohumoral response of vasopressin â renin-angiotensin-aldosterone system. Vasopressin and norepinephrine play significant role in causing damage to hepatic function.
In this study, of the 60 patients who constituted the study population, 45 were female patients and 15 were male. All patients were between 15 and 75 years of age. Majority of patients were below 50 years (i.e. 54 patients). Patients who underwent various types of laparoscopic surgeries were included in the study. 23 patients were operated for acute appendicitis, of which one patient also had associated appendiceal perforation peritonitis, they all underwent laparoscopic appendicectomy. Patient with peritonitis also underwent peritoneal toilet. Laparoscopic cholecystectomy was done in 16 patients, mostly for calculous cholecystitis. Gynaecologic surgeries were also included in the study of which majority were laparoscopic assisted vaginal hysterectomy, done in 15 patients. In this 2 patients underwent salpingoopherectomy along with LAVH. Ovarian cysterectomy was done in 3 patients. Testicular vein ligation was done in 1 patient with varicocoele. 2 patients, who presented with subacute intestinal obstruction due to post-op adhesions, underwent laparoscopic adhesiolysis.
In all patients, levels of serum bilirubin, serum AST, serum ALT and serum alkaline phosphatase were checked preoperatively once and post operatively on day 1 and day 7. In detail, mean level of serum bilirubin preoperatively was 0.70 +/- 0.14mg/dL. Postoperatively on day 1 and day 7 the levels were 1.10 +/- 0.32mg/dL and 0.75 +/- 0.18mg/dL respectively. Thus, it was found that there was a significant rise (P=0.001) in serum bilirubin levels in the immediate post-op period which came down to near pre-op values within 1 week postoperatively.
Similarly, mean level of serum AST pre-operatively was 19.52 +/- 15.99U/L. Post-operatively day 1 and day 7 the levels were 30.13 +/-9.80 U/L and 19.97 +/- 5.26 U/L respectively. There was a significant rise (P=0.001) in serum AST levels in the immediate post-op period when compared to pre-op values, which came down to near pre-op values with in a weeksâ time.
The mean level of serum ALT preoperatively was 22.56 +/- 5.09 U/L. Postoperatively day 1 and day 7 the levels were 38.63 +/- 12.17 U/L and 25.45 +/- 5.94 U/L respectively. Here again, there was a significant rise (P =0.001) in serum ALT levels in immediate post-op period when compared to pre-op values. The levels came down to near pre-op values by post-op day 7. The mean level of serum Alkaline phosphatase pre-operatively was 103.81 +/- 23.30 U/L. Post operatively on day 1 and day 7 the mean levels were 147.71 +/- 36.50 U/L and 108.01 +/- 21.92 U/L respectively. A significant rise (P=.001) was seen in post-op day 1 level of serum alkaline phosphatase values when compared to the pre-op level. This came down to near pre-op values within a week of postoperative period.
The transient post operative increases in serum bilirubin and liver enzyme levels were seen in study population, irrespective of the type of laparoscopic surgery they underwent. It was also noticed that post-op day 1 level doubled the pre-op values in 20% patients in case of serum bilirubin. 33.3% patients had doubling of serum AST levels and 31.7% had doubling of serum ALT levels. Serum Alkaline phosphatase levels doubled only in 16.7% patients. These increased levels were seen in those patients who had a prolonged period of CO2 pneumoperitoneum when compared to others. In all the patients where there was a transient rise in the enzyme levels, values returned to near-pre-operative concentrations within one week after surgery. None of the patients presented with clinical hepatic dysfunction after surgery according to follow up observations and feedback from these patients.
Studies done by other authors (26), (27), (28) also revealed similar findings and they have concluded that the transient elevation of hepatic enzymes occurred after laparoscopic surgery. Major causative factor seemed to be CO2 pneumoperitoneum. In most of the laparoscopic surgery patients, transient elevation of serum liver enzymes showed no apparent clinical implications.
In accordance with earlier studies we conclude that if patientsâ pre-operative liver function is very poor, laparoscopic surgery might not be the optimal choice for treating certain abdominal diseases. Recent studies done by Giraudo G, Brachet Contul R et al (29) suggest that recent advances in laparoscopic surgery like gasless laparoscopy can avoid causing alterations in hepatic function. So, this could be tried as an alternative to routine laparoscopic surgeries using CO2 pneumoperitoneum, in patients with poor liver function.
From this study, we conclude that all types of laparoscopic procedures can cause transient elevation of hepatic enzymes and serum bilirubin for which the major causative factor seems to be CO2 pneumoperitoneum.
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