Effects of Varying Intraperitoneal Pressure on Liver Function Tests During Laparoscopic Cholecystectomy

Abstract

Background:

Laparoscopic cholecystectomy at standard-pressure pneumoperitoneum uses a pressure of 12–14 mm Hg, which may cause a variety of adverse physiological changes involving the respiratory, cardiovascular, and hepatorenal systems reflected as subclinical abnormalities in biochemical parameters. The use of low-pressure pneumoperitoneum in the range of 8–10 mm Hg has been shown to reduce the adverse physiological changes without affecting the outcome of surgery.

Subjects and Methods:

This study was done in a randomized controlled manner. Patients with gallstone disease (n=101) underwent laparoscopic cholecystectomy. Patients were randomly assigned to high-pressure laparoscopic cholecystectomy (HPLC) (n=51) and low-pressure laparoscopic cholecystectomy (LPLC) (n=50) and underwent surgery at pressures of 14 mm Hg and 8 mm Hg, respectively. Liver function tests, including total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase, were obtained preoperatively and on postoperative Days 1 and 7.

Results:

The two study groups had similar demographic profiles, and there were no significant differences in the operative time (HPLC, 47.25±6.73 minutes; LPLC, 48.00±7.76 minutes; P=.6071) and pneumoperitoneum time (HPLC, 34.02±5.29 minutes; LPLC, 34.60±6.13 minutes; P=.6115). On postoperative Day 1, the total bilirubin levels were 1.0684±0.4108 mg/dL and 0.8926±0.3162 mg/dL for HPLC and LPLC (P=.0179), respectively, AST levels were 66.0810±25.5868 IU/L and 42.2420±14.7301 IU/L (P=.0001), respectively, and ALT levels were 68.1410±31.4572 IU/L and 42.7460±17.9405 IU/L (P=.0001), respectively. Thus, liver enzyme activities were significantly elevated in the HPLC group compared with the LPLC group.

Conclusions:

LPLC causes less abnormality in liver function tests in the postoperative period compared with HPLC. LPLC should be considered in all patients undergoing laparoscopic cholecystectomy, especially those patients with compromised liver functions.

Introduction

Laparoscopic cholecystectomy (LC) is the gold standard for the management of gallstone disease.^1,2 LC requires working space in the abdomen, which is produced by insufflating CO₂ up to a pressure of 12–14 mm Hg, which is considered as standard.^1,2 CO₂ insufflation at this pressure, however, causes a variety of adverse physiological changes involving the respiratory, cardiovascular, and hepatorenal systems as well as increased risk of deep venous thrombosis.^3–7 Most of these subtle changes are only reflected as subclinical abnormalities in biochemical parameters.⁸ Feasibility of LC at a low intraperitoneal pressure of 8–10 mm Hg has been well documented in the literature.^9–11 This study aims to compare the effect of two different peritoneal pressures on postoperative derangement of liver function tests (LFTs) after LC in a prospective randomized manner.

Patients and Methods

This study included 101 patients with uncomplicated gallstone disease and was conducted in the Department of General Surgery at the Post Graduate Institute of Medical Education and Research, Chandigarh, India, over a period of 1 year, from January 2011 to December 2011, after approval was obtained from the bioethical committee of the Institute.

Both male and female patients between 18 and 70 years of age with normal preoperative LFTs who were fit for laparoscopy were included in this study. Preoperative hemograms, LFTs, renal function tests, abdominal ultrasounds, electrocardiograms, and chest X-rays were done for all patients to confirm the diagnosis of uncomplicated gallstone disease and also to assess the fitness for laparoscopy surgery. Patients with a history of jaundice, with common bile duct stones, or with abnormal preoperative LFTs were excluded from this study.

Patients were randomly divided into two groups by the sealed envelope method: one with standard pressure, where pressure during LC was 14 mm Hg (HPLC), and another with low pressure, where pressure during LC was 8 mm Hg (LPLC).

Standard anesthetic technique was used. All patients were operated on by either of two experienced laparoscopic surgeons. Patients were operated by the standard American technique of four-port LC. The abdomen was insufflated using CO₂, and patients were kept in the reverse Trendelenburg position. Monopolar electrocautery was used in both groups to dissect the gallbladder from the liver bed. The operating surgeon had the full liberty to increase the intra-abdominal pressure from low pressure (8 mm Hg) to high pressure (14 mm Hg) if he thought that the operative field was not adequate. He also had the liberty to convert LC to open cholecystectomy in the case of difficult gallbladder dissection risking the completion of the laparoscopic procedure or excess bleeding that could not be controlled by laparoscopic techniques. Conversion of LPLC to HPLC was considered as a failure of LPLC, and conversion of LC to open cholecystectomy was considered as a failure of HPLC or LPLC.

Patients were allowed oral intake 6 hours after surgery and were discharged either on the same day as the day-surgery basis or on the first postoperative day (POD) after ensuring satisfactory general condition and oral intake. LFTs (serum total bilirubin, aspartate transaminase [AST], alanine transaminase [ALT], and alkaline phosphatase) were done on POD 1 and POD 7 as it was convenient to have LFTs done on follow-up visits or before discharge from the hospital. All the investigations were done in the biochemistry laboratory of the Institute.

Statistical analysis

Descriptive statistics were used. Data were expressed in terms of mean±standard deviation values. Differences between the two groups were determined by Student's unpaired t test for continuous scale variables and by Fisher's exact test for categorical variables. All P values of <.05 were considered statistically significant. All data were analyzed with SPSS (Statistical Package for Social Sciences) software (version 16.0; SPSS, Inc., Chicago, IL).

Results

One hundred one patients gave consent and qualified for the study as per the inclusion and exclusion criteria. LC was done as HPLC in 51 patients and as LPLC in 50 patients. No patients were excluded from any of the two groups because of conversion from LPLC to HPLC or LC to open cholecystectomy. The two study groups were analyzed with respect to age, gender, operative time, and pneumoperitoneum time (Table 1). LFTs performed preoperatively and also on POD 1 and POD 7 were compared in the HPLC and LPLC groups (Table 2). Bilirubin, AST, and ALT levels were significantly higher on POD 1 in the HPLC group (P=.0179, .0001, and .0001, respectively) but normalized on POD 7 (Table 2).

Table 1.

Characteristics of Patients in the High-Pressure Laparoscopic Cholecystectomy and Low-Pressure Laparoscopic Cholecystectomy Groups

Clinical data	HPLC group	LPLC group	P value	Significance
Number of patients	51	50	—	—
Sex (male/female)	11/40	10/40	1	NS^a
Age (years) (mean±SD)	44.67±14.23	43.46±11.40	.6396	NS^b
Pneumoperitoneum time (minutes) (mean±SD)	34.02±5.29	34.60±6.13	.6115	NS^b
Operative time (minutes) (mean±SD)	47.25±6.73	48.00±7.76	.6071	NS^b

By Fisher's exact test.

By unpaired Student's t test.

HPLC, high-pressure laparoscopic cholecystectomy; LPLC, low-pressure laparoscopic cholecystectomy; NS, not significant; SD, standard deviation.

Table 2.

Liver Function Tests in the High-Pressure Laparoscopic Cholecystectomy and Low-Pressure Laparoscopic Cholecystectomy Groups

Test	Preoperative	P value^a	Postoperative Day 1	P value^a	Postoperative Day 7	P value^a
Total bilirubin (mg/dL)		.0639		.0179		.6441
HPLC (n=51)	0.5492±0.1758		1.0684±0.4108		0.5759±0.1771
LPLC (n=50)	0.6208±0.2070		0.8926±0.3162		0.5924±0.1812
AST (IU/L)		.3314		.0001		.0814
HPLC (n=51)	27.8276±5.8857		66.0810±25.5868		29.5892±5.6371
LPLC (n=50)	26.6662±6.0733		42.2420±14.7301		27.5816±5.8219
ALT (IU/L)		.1811		.0001		.1146
HPLC (n=51)	28.0780±6.7413		68.1410±31.4572		30.4610±5.7533
LPLC (n=50)	26.2064±7.2199		42.7460±17.9405		28.3742±7.3402
ALP (IU/L)		.8201		.3899		.6439
HPLC (n=51)	87.059±18.333		81.94±17.66		83.45±18.43
LPLC (n=50)	87.886±18.126		84.76±15.00		81.82±16.87

Data are mean±standard deviation values.

By unpaired Student's t test. P values <.05 designate significant differences.

ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HPLC, high-pressure laparoscopic cholecystectomy; LPLC, low-pressure laparoscopic cholecystectomy.

Discussion

LC is the gold standard procedure for management of gallstone disease. Pneumoperitoneum created during LC elevates the diaphragm and decreases the lung compliance.^4,12 It also decreases the venous return to the heart, which subsequently decreases the stroke volume and cardiac output. This decrease in cardiac output further decreases the renal, splanchnic, and hepatoportal blood flow.^5,12,13 One important effect of pneumoperitoneum is venous stasis of the lower limb, which is further aggravated by the reverse Trendelenburg position.^7,12 Another issue is the abnormalities of the LFTs after LC. This becomes more important in patients with chronic liver disease like fatty liver and cirrhosis who have to undergo laparoscopic procedures.

Since the introduction of laparoscopic surgery, efforts have been made to reduce the adverse hemodynamic and cardiopulmonary effects of pneumoperitoneum without compromising the efficacy, feasibility, and safety of the operation.^10,14–17 Various techniques of LC have evolved either by using low-pressure pneumoperitoneum or by using the gasless technique during laparoscopy.^9,10,17 Gasless laparoscopy has been shown to cause fewer abnormalities in LFTs compared with HPLC, but its superiority over LPLC has not been proved. Additionally, the quality of exposure in the gasless techniques is not as good as with pneumoperitoneum.¹⁸ Safety of LPLC has been established by many clinical studies in terms of feasibility of procedure and fewer hemodynamic effects on peritoneal insufflation.^9,14,19,20 It has additional benefits of less postoperative and shoulder-tip pain, shorter hospital stay, and a better quality of life within 5 days following the operation.^14,16,19,21

A transient increase in serum transaminase activities has been reported by various studies after HPLC that returns to normal levels within 3 days after surgery.^8,22–25 It has been suggested that increased intraperitoneal pressure, compression of the liver by cranial retraction of gallbladder during LC, cauterization of the liver bed for hemostasis, manipulation of external bile ducts, and effects of general anesthesia cause elevation of liver enzyme activities.²⁶ Intraoperative Doppler ultrasound study has shown a 53% reduction in portal blood flow with a intraperitoneal pressure of 14 mm Hg.²⁷ This might also explain the transient abnormalities of LFTs after LC. Intraperitoneal pressure of 14 mm Hg is higher than the normal portal blood pressure of 7–10 mm Hg, which might reduce portal blood flow and cause alteration in LFTs.²⁸ There is also the suggestion of “ischemia and reperfusion” injury during laparoscopic procedures due to rapid changes in intraperitoneal pressure as the cause of alteration of LFTs.²⁹

The effects of low-pressure pneumoperitoneum on LFTs has not been studied, but after understanding the effects of standard-pressure pneumoperitoneum on hepatoportal physiology, a positive effect of low-pressure pneumoperitoneum can be reasonably anticipated. Other experimental and clinical studies have demonstrated pneumoperitoneum-induced hepatic hypoperfusion, which is compatible with the hypothesis of intra-abdominal hypertension-induced ischemic injury to the hepatocytes.^26–32 Our study has shown a significant difference in LFTs on POD 1 in the HPLC group compared with the LPLC group that normalized on POD 7. The interesting point is the significance of this transient abnormality of the LFTs and its bearing on the clinical outcome. In our study no patient had any clinical morbidity because of the HPLC, and in follow-up they did not need any further investigations for abnormal LFTs. But, this may be more relevant in patients with chronic liver disease like cirrhosis. This aspect needs to be investigated.

In conclusion, this study concludes that low-pressure pneumoperitoneum causes less alteration of hepatoportal physiology, which is reflected in terms of nearly normal liver functions in the postoperative period compared with high-pressure pneumoperitoneum. We recommend using low-pressure pneumoperitoneum wherever feasible to decrease the hemodynamic variations and also to add on to already existing benefits of endoscopic surgery.

Footnotes

Disclosure Statement

No competing financial interests exist.

References

Joris

, Cigarini

, Legrand

et al. Metabolic and respiratory changes after cholecystectomy performed via laparotomy or laparoscopy. Br J Anaesth, 1992; 69:341–345.

Berggren

, Gordh

, Grama

et al. Laparoscopic versus open cholecystectomy: Hospitalization, sick leave, analgesia and trauma responses. Br J Surg, 1994; 81:1362–1365.

Baraka

, Jabbour

, Hammoud

et al. End tidal carbon dioxide tension during laparoscopic cholecystectomy. Anaesthesia, 1994; 49:304–306.

Bardoczky

, Engelman

, Levarlet

et al. Ventilatory effects of pneumoperitoneum monitored with continuous spirometry. Anaesthesia, 1993; 48:309–311.

Noirot

, Joris

, Legrand

et al. Hemodynamic changes during pneumoperitoneum for laparoscopic cholecystectomy. Anaesthesia, 1992; 77:69.

Dexter

SPL

, Vucevic

, Gibson

et al. Hemodynamic consequences of high and low-pressure capnoperitoneum during laparoscopic cholecystectomy. Surg Endosc, 1999; 13:376–381.

Beebe

, McNevin

, Crain

et al. Evidence of venous stasis after abdominal insufflation for laparoscopic cholecystectomy. Anaesthesia, 1992; 77:148.

Saber

, Laraja

, Nalbandian

et al. Changes in liver function tests after laparoscopic cholecystectomy: Not so rare, not always ominous. Am Surg, 2000; 66:699–702.

Davides

, Birbas

, Vezakis

et al. Routine low-pressure pneumoperitoneum during laparoscopic cholecystectomy. Surg Endosc, 1999; 13:887–889.

10.

Wallace

, Serpell

, Baxter

et al. Randomized trial of different insufflation pressures for laparoscopic cholecystectomy. Br J Surg, 1997; 84:455–458.

11.

Kar

, Kar

, Debnath

. Experience of laparoscopic cholecystectomy under spinal anesthesia with low-pressure pneumoperitoneum—Prospective study of 300 cases. Saudi J Gastroenterol, 2011; 17:203–207.

12.

Neudecker

, Sauerland

, Neugebauer

et al. The European Association for Endoscopic Surgery clinical practice guideline on the pneumoperitoneum for laparoscopic surgery. Surg Endosc, 2002; 16:1121–1143.

13.

Eleftheriadis

, Kotzampassi

, Botsios

et al. Splanchnic ischemia during laparoscopic cholecystectomy. Surg Endosc, 1996; 10:324–326.

14.

Barczyński

, Herman

. A prospective randomized trial on comparison of low-pressure (LP) and standard-pressure (SP) pneumoperitoneum for laparoscopic cholecystectomy. Surg Endosc, 2003; 17:533–538.

15.

Barczyński

, Herman

. The usefulness of low-pressure pneumoperitoneum in laparoscopic surgery. Folia Med Cracov, 2002; 43:43–50.

16.

Sarli

, Costi

, Sansebastiano

et al. Prospective randomized trial of low-pressure pneumoperitoneum for reduction of shoulder-tip pain following laparoscopy. Br J Surg, 2000; 87:1161–1165.

17.

Giraudo

, Brachet

, Caccetta

et al. Gasless laparoscopy could avoid alterations in hepatic function. Surg Endosc, 2001; 15:741–6.

18.

Vezakis

, Davides

, Gibson

et al. Randomized comparison between low-pressure laparoscopic cholecystectomy and gasless laparoscopic cholecystectomy. Surg Endosc, 1999; 13:890–893.

19.

Joshipura

, Haribhakti

, Patel

et al. A prospective randomized, controlled study comparing low pressure versus high pressure pneumoperitoneum during laparoscopic cholecystectomy. Surg Laparosc Endosc Percutan Tech, 2009; 19:234–240.

20.

Catani

, Guerricchio

, De Milito

et al.

“Low-pressure” laparoscopic cholecystectomy in high-risk patients (ASA III and IV): Our experience [in Italian]

Chir Ital, 2004; 56:71–80.

21.

Sandhu

, Yamada

, Ariyakachon

et al. Low-pressure pneumoperitoneum versus standard pneumoperitoneum in laparoscopic cholecystectomy, a prospective randomized clinical trial. Surg Endosc, 2009; 23:1044–1047.

22.

Tan

, Xu

, Peng

et al. Changes in the level of serum liver enzymes after laparoscopic surgery. World J Gastroenterol, 2003; 9:364–367.

23.

Guven

, Oral

. Liver enzyme alterations after laparoscopic cholecystectomy. J Gastrointestin Liver Dis, 2007; 16:391–394.

24.

Saber

. Non ominous changes in liver function tests after laparoscopic cholecystectomy. J Gastrointestin Liver Dis, 2007; 16:427–428.

25.

Marakis

, Pavlidis

, Ballas

et al. Alterations in liver function tests following laparoscopic cholecystectomy. Internet J Surg, 2006; 8,1 10.5580/b66.

26.

Halevy

, Gold-Deutch

, Negri

et al.

Are elevated liver enzymes and bilirubin levels significant after laparoscopic cholecystectomy in the absence of bile duct injury?

Ann Surg, 1994; 219:362–364.

27.

Jakimowicz

, Stultiens

, Smulders

. Laparoscopic insufflation of the abdomen reduces portal venous flow. Surg Endosc, 1998; 12:129–132.

28.

Schmandra

, Kim

, Gutt

. Effect of insufflation gas and intraabdominal pressure on portal venous flow during pneumoperitoneum in the rat. Surg Endosc, 2001; 15:405–408.

29.

Volz

, Koster

, Spacek

, Paweletz

. Characteristic alterations of the peritoneum after carbon dioxide pneumoperitoneum. Surg Endosc, 1999; 13:611–614.

30.

Mucke

, Richter

, Menger

et al. Significance of hepatic arterial responsiveness for adequate tissue oxygenation upon portal vein occlusion in cirrhotic livers. Int J Colorectal Dis, 2000; 15:335–341.

31.

Richter

, Vollmar

, Mucke

et al. Hepatic arterioportal venous shunting guarantees maintenance of nutritional microvascular blood supply in hepatic arterial buffer response of rat livers. J Physiol (Lond), 2001; 531:192–201.

32.

Richter

, Olinger

, Hildebrandt

et al. Loss of physiologic hepatic blood flow control (“hepatic arterial buffer response”) during CO₂-pneumoperitoneum in the rat. Anesth Analg, 2001; 93:872–877.