Effects of capnoperitoneum on liver functions: A comparison between biliary and non-biliary laparoscopic surgeries.

Background Capnoperitoneum during laparoscopy alters liver enzyme activity which is subclinical and goes undiagnosed most of the times, but may lead to life threatening complications in patients with compromised hepatic functions. Studies on altered hepatic enzyme activity have been conducted on patients undergoing laparoscopic cholecystectomy and seldom on laparoscopic non biliary surgeries which we encounter daily. Hence aim of study was to compare the effects of capnoperitoneum on liver functions in biliary and non biliary surgeries. Methodology This prospective clinical observational study was conducted on 60 patients undergoing elective laparoscopic surgeries after obtaining institutional ethics committee clearance. Patients were divided into biliary and non biliary group consisting of 30 patients in each group. Patients’ blood samples were collected preoperatively and 24 hours postoperatively for accessing liver enzymes. Statistical analysis done using SPSS version 23. Shapiro-wilk, paired ‘t’ and chi-square tests were used to analyse the data. P < 0.05 considered statistically significant.


Introduction
Laparoscopy is a minimally invasive surgery to access organs and structures of abdominal cavity 1 .Laparoscopic cholecystectomy is considered as the gold standard method to treat uncomplicated cholelithiasis 2,3 .Capnoperitoneum is creating pneumoperitoneum with carbon dioxide.This causes an elevation in the intra-abdominal pressure and also continuously compresses intra-abdominal organs and elevates the diaphragm which might potentially influence the hepatic, pulmonary and renal functions 4 .Numerous recent articles have shown that the level of serum liver enzymes rise significantly following laparoscopic procedures which might be attributed to altered hepatic and splanchnic circulation 4 .Pneumoperitoneum, increased intraabdominal pressure more than 14mmHg, the undulation and re-irrigation of organs causing ischaemia, squeeze pressure effect on liver and use of diathermy, duration of surgery more than 60 minutes are some of the other factors which are known to cause alteration of liver enzymes in postoperative period 5,6 .There are very few studies showing the effects of capnoperitoneum in specific non-biliary laparoscopic surgeries.Hence the primary objective was to compare the effects of capnoperitoneum on liver functions in biliary and non-biliary surgeries.

Methodology
After obtaining approval from the institution ethics committee, 60 patients of either sex who fulfilled the inclusion and exclusion criteria were considered for this prospective observational study.Clinical trial was registered [CTRI no: CTRI/2020/11/029416].This study was conducted in accordance with 2013-Helsinki Declaration.Sample size was estimated using incidence in previous studies at 95% confidence interval and 80% power considering 10% nonresponse a sample size of 30 patients was required in each group.Written informed consent was obtained from all patients taking part in the study.Computerised randomisation of patients was done.Patients between 18-60 years with ASA physical status 1 and 2 posted for elective biliary surgeries like laparoscopic cholecystectomy and nonbiliary surgeries like laparoscopic umbilical hernia, laparoscopic ovarian cystectomy and laparoscopic inguinal hernia were included in the study.Whereas patients with co-existing liver diseases, having altered liver enzymes, history of previous major abdominal surgeries, surgeries extending for a duration of more than 2 hours, cases converted from laparoscopic to open, pregnant and lactating women were excluded from the study.
All participants were pre-operatively evaluated.Liver functions were estimated on the previous day of surgery.On shifting to operating room, baseline vital parameters were recorded after connecting standard monitors.All patients received general anaesthesia as per standard institutional protocol.Premedicated with intravenous glycopyrrolate 5µg/kg and intravenous midazolam 0.05 mg/kg.Fentanyl 2μg/kg was given as analgesic.Induced with injection propofol 2 mg/kg and relaxed with injection atracurium 0.5 mg/kg and intubated using appropriate size cuffed endotracheal tube.The depth of anaesthesia was maintained with oxygen, nitrous oxide and sevoflurane.Intermittently relaxed with injection atracurium 0.1 mg/ kg.The time of induction and incision were noted.Abdomen was insufflated with carbon dioxide and the time of insufflation was noted.The insufflation pressure was set and maintained at 12-15mmhg.The haemodynamic parameters were monitored every 10 minutes throughout the procedure.Post-procedure the abdomen was deflated and the total duration of capnoperitoneum was noted.Patient was extubated smoothly after reversing the residual neuromuscular blockade.Then patients were shifted to post anaesthesia care unit.Post operatively fluids were transfused at 75ml/kg for 24hours to exclude haemodilution effects.

Outcome measures:
For the primary outcome liver function test was repeated 24 hours post surgery and compared with the preoperative values.The difference in derangement of various parameters in liver functions were noted.The degree of variation of these enzymes was compared in both biliary and non-biliary surgeries and the outcome was tabulated.operative albumin values were 4.03±0.52 and 3.55±0.66respectively with p value < 0.001.There is no statistically significant difference between the pre operative and post operative values with respect to aspartate transaminase, alanine transaminase and gamma glutamyl transferase.

DISCUSSION
Laparoscopic surgeries have taken over the traditional open techniques in the last two decades.The advantage being minimally invasive, decreased duration of hospital stay, small incision, better haemodynamic stability, early return to normalcy, less tissue damage and reduced morbidity rate. 7ough carbon dioxide is the best insufflation gas till date it might cause systemic side effects like hypercarbia, acidosis, hemodynamic instability etc. when used for prolonged durations.right atrium hence reducing cardiac output. 6,9Intra abdominal insufflation pressures of 12-15 mmHg which is higher than portal pressures of 7-10 mmHg have been shown to reduce splanchnic circulation and hepatic perfusion leading to altered liver enzyme activity. 4,10Other cause for altered enzyme activity could be the frequent rise and fall of intra abdominal pressure that causes ischaemia and reperfusion of the liver which in turn damages the endothelium, hepatic sinusoids and Kupffer cells. 5,11The use of diathermy for cautery and coagulation may cause heat-induced damage to the hepatic parenchyma which may explain the altered hepatic enzyme levels after the procedure. 6,12,13 is well known that general anaesthesia causes hepatic hypoperfusion and thus alters enzymatic activity.Surgical duration of more than 60 minutes, prolonged handling and retraction of abdominal viscera, the squeeze effect on the liver, undulation and irrigation with saline into the cavity and clipping of the right branch of the hepatic artery all cause significant alterations in hepatic enzymes. 14,15n biliary surgeries the variations in liver enzymes may be as a result of squeeze effect on the liver, clipping of hepatic artery, prolong handling and retraction of gall bladder, undulation and reirrigation of blood flow leading to ischaemia and injury of abdominal organs. 16,17The other probable reasons for variation in hepatic enzymes are liver retraction done for better exposure, manipulation of biliary tract for detecting possible common bileduct stones, electrocauterization of the liver bed to achieve haemostasis along with capnoperitoneum.
In non biliary surgeries the causes for altered liver enzyme activity could be general anaesthesia, pneumoperitoneum, electrocautery, prolonged duration of surgery [>60minutes] and handling of abdominal viscera. 5 our study the demographic data, ASA status, duration of capnoperitoneum and duration of surgery were statistically not significant between the biliary and non biliary groups.
In our biliary group we have found a statistically significant increase in total bilirubin, direct bilirubin, alkaline phosphatase, whereas a marginal increase was found in aspartate transaminase and alanine transaminase.Our results are in comparison with other studies. 5,12,18,19ellad A and Sahu K. 5 have observed a significant decrease in the levels of serum albumin and total proteins during the first 24 hours in their study.We have also observed statistically significant decrease in total protein and albumin in our biliary group.
All these variations in liver enzymes are transient and return back to normal levels within 48-72 hours.Halevy et al 12 and Morino et al 19 stated that the elevated AST, ALT and total bilirubin returned to normalcy within 72 hours after the surgery.
In our non-biliary group we noticed an alteration in liver enzymes.The elevation in aspartate transaminase, alkaline phosphatase was statistically significant whereas there was moderate elevation in total bilirubin and direct bilirubin.This may be due to the effect of capnoperitoneum alone or the effects of diathermy/electrocautery in addition. 19e also observed statistically significant decrease in total protein and albumin.
The increase in total and direct bilirubin amongst biliary group are specific to liver insult /injury while increase in the aminotransferases amongst the non biliary group is non specific to liver insult/injury as it is found increased in injury of other organ like heart, skeletal muscle, kidney, bone etc. 20 Post operative fall in albumin levels is an indication of surgical stress. 5In both the groups we observed a significant decrease in post operative total protein and albumin due to surgical trauma.
There are certain limitations in our study, the sample size was small and limited to our institution.The other limitations are the requirement of serial LFTs at 48-72 hrs to validate results done in multiple other studies, considering position of patient as liver blood flow is altered in trendelenburg or reverse Trendelenburg positions and need to estimate the blood loss which could have significant effect on LFT.

CONCLUSION
In this study we have observed that capnoperitoneum altered the post operative liver biomarkers in both laparoscopic biliary and non biliary surgeries but elevation of biomarkers specific to liver injury were found in biliary group which may be due to additional factors like retraction, manipulation of biliary tract, cauterization of liver bed.

FIGURE 1 :
FIGURE 1: Pre and post operative variables in biliary group.X axis: different enzymes.Y axis: estimates of enzymes.

FIGURE 2 :
FIGURE 2: Pre and post operative variables in non biliary group.X axis: different enzymes ; Y axis: estimates of enzymes.

Table 1 :
RESULTSAll the 60 patients completed the study.Majority of subjects were in the age group of 21-50 years [60%].There is no significant difference between the two groups with respect to age, gender, ASA status, duration of capnoperitoneum and duration of surgery [Table1].In biliary and non-biliary groups the mean age of the patients was 41.73±13.66 and 41.2±15.98 (p=0.8)respectively.Demographic data.Values are presented in mean ± standard deviation.ASA-American Society of Anesthesiologists.

Table 2 :
Comparison of pre and post operative liver enzymes in biliary group.Values are presented in mean ± standard deviation.CI-Confidence Interval.* Indicates statistical significance.

Table 3 :
Comparison of pre and post operative liver enzymes in non biliary group.Values are presented i n mean ± standard deviation.C.I -Confidence Interval.* indicates statistical significance.