Out of abdominal surgeries, cholecystectomy is one of the most common to be performed. Laparoscopic cholecystectomy is considered the "gold standard" procedure for the surgical therapy of cholelithiasis ( 1 ). It is considered to be as safe as open cholecystectomy, however, with a certain number of added advantages ( 2 ). This procedure has the advantage of better cosmesis, relatively short duration of hospital stay, lesser inability from work and reduced post-operative painthan open cholecystectomy ( 3 ). Subsequently, it results in less prominent stress response and metabolic interference when contrastedwithopen cholecystectomy ( 4 ). Meticulous technique, careful case selection, better training, and high standard equipment of central significance is necessary for good outcomes in laparoscopic cholecystectomy ( 5 ). Hence, the development of laparoscopic cholecystectomy revolutionized the history of biliary surgery ( 6 ). It is safe and effective management of gall stone disease. It has moved the focus of surgery towards reducing the morbidity without compromising on the quality of healthcare ( 7 ). Also, it is the most commonly performed laparoscopic procedure in developing countries. While laparoscopic cholecystectomy is, for the most part, thought to be less painful than open surgery, pain is one of the essential reasons behind deferred discharge from the hospital after surgery and overnight stay.

Advancements in the understanding and treatment of gallstones have been rapid amid the previous decade. Decades-long excellent quality of open surgical cholecystectomy as a treatment for gallstones has been tested by gallstone-disintegration methods and shock-wave lithotripsy and has been ousted by laparoscopic cholecystectomy ( 8 ). Therefore a laparoscopiccholecystectomy not only provides a standard treatment of cholelithiasis, it is further being improvised so that this procedure not only has less morbidity for the patient but also is more efficient in term of hospital costs and patient turn over. Currently, different studies are being carried out in many parts of the world to still optimize this much-developed procedure so laparoscopic cholecystectomy could be established as a standard day case surgery ( 9 ).

The main focus of these studies is to provide better pain management to the patient by effective on-site analgesia, reducing pneumo peritoneum pressure and infiltrating the wound with local anesthetic agents ( 10 ). After that, this study was carried out in light with the aim to evaluate the effectiveness of instillation of Bupivacaine at peri-trocar, gall bladder, and sub-hepatic space after elective laparoscopic cholecystectomy on post-op pain, analgesia demand, early mobility, and hospital stay. Determining the outcome in these two groups will allow the surgeons to perform laparoscopic cholecystectomy as a day-case surgery by keeping patient pain free and thus achieving early discharge, early return to function, short hospital stay, a better patient turn-over and after that the costs on hospital resources.

The hospital ethical committee first approved the work plan. All patients admitted with cholelithiasis to the surgical unit of Pakistan Institute of Medical Sciences Islamabad were enrolled in the study as per inclusion criteria. Written informed consent was obtained from the patient. A detailed medical history was obtained from patients in which patients were asked questions about their demographic data, history of presenting illness, past medical history, drug history, history of previous medical and surgical procedures as well as occupational and travel history. The history concluded by a systematic review. History taking followed physical examination. Then investigations were carried out to confirm the diagnosis of symptomatic gall stones, polyp or sludge.

After planning surgery, patients were assessed by the Department of Anesthesiology and other relative departments for co-morbid if present, e.g. diabetes mellitus, hypertension or asthma for optimal fitness for surgery. In Group A, after laparoscopic cholecystectomy, on the final stage of closure, peritrocal, subphrenic and gallbladder bed instillation of bupivacaine (0.125%) was done. In group B no such intervention was done. After the surgery, a meticulous record of the treatment was kept. The parietal, visceral, and shoulder tip pain was assessed at 4, 8, 12 and 24 hours post operatively using a visual analog scale (VAS). Intravenous tramadol 50mg (1ml) diluted in 9 ml of normal saline was used as analgesia. The time for the first demand of analgesia, the frequency of the demand by the patient, time to mobility in hours after surgery and post-op hospital stay was also recorded. All data were collected by the postgraduate resident and was documented on the Performa.

A total of 164 patients included in the study. Out of these, 82 patients who underwent a laparoscopic cholecystectomy as control subjects 14 were male, and 68 were female. While 82 patients who underwent laparoscopic cholecystectomy followed by Bupivacaine instillation 19 were male and 63 were female. The mean age of patients in the control group was 48.46 years with standard deviation of 9.17. The youngest patient was 32 years old and oldest was 68 years old with 53.7% of these patients falling up to 50 years of age. While mean age of patients in the group of bupivacaine instillation was 49.5 with a standard deviation of 7.8; the youngest being 31 years old and oldest 65 years old with 50% of these patients falling up to 50 years of age (Table-1). Among the control group, upon assessment for pain by VAS at 4 hours, the mean VAS was 3.3 with standard deviation of 1.08 with a max score of 6 and minimum of 1. while in group with bupivacaine instillation mean VAS at 4 hours was 0.94 with a standard deviation of 0.89 with a Maximum score of 3 and Minimum of 0. The mean VAS assessed at 8 hours in the control group was 4.84 with a standard deviation of 1.52 with a maximum score of 8 and a minimum of 1. While in the group with bupivacaine instillation mean VAS at 8 hours was 1.06 with a standard deviation of 0.83 with a maximum score of 4 and a minimum of 0. The mean VAS assessed at 12 hours in the control group was 5.07 with a standard deviation of 1.32 with a maximum of 8 and a minimum of 2. While in a group with bupivacaine instillation mean VAS at 12 hours was 1.39 with a standard deviation of 1.063 with a maximum score of 5 and a minimum of 0. The mean VAS assessed at 24 hours in the control group was 5.76 with a standard deviation of 1.38 with a maximum score of 8 and a minimum of 2. While in a group with bupivacaine instillation mean VAS at 24 h was 1.34 with a standard deviation of 0.96 and a maximum score of 2 and a minimum of 0. The most common first site of pain in control group was operation site as reported by 55 (67.1%) patients in that group; followed by shoulder pain in 18 (22%) patients, pain at other sites in 6 (7.3%) followed by visceral in 3 (3.7%) patients. The most common first site of pain in bupivacaine instillation group was operation site as reported by 35 (42.7%) patients in that group; followed by visceral in 30 (36.6%) patients, pain at other sites in 9 (11%) followed by shoulder pain in 8 (9.8%) patients.

During the hospital stay all 82 patients in the control group required analgesia. However, in a group with bupivacaine instillation 33 out of 82 patients required analgesia. The first dose of analgesia required by a patient of the control group was at an average of 7.48 hours after surgery with a standard deviation of 1.39. While in bupivacaine instillation group the first dose of analgesia required was at 6.39 hours with a standard deviation of 5.05 hours. The patients in the control group required their first dose as early as 06 hours and a latest by 10 hours after surgery. Meanwhile, the patients in the control group required their first dose as early as 08 hours and a latest by 24 hours after surgery. All 82 (100%) patients in the control were administered analgesia within 06-10h. However out of 33 (40.2%) patients that required analgesia in bupivacaine instillation group 15 (18.3) required analgesia within 16-20 hours, 7(8.5%) in 21-25 hours, 6 (7.3%) in 06-10 hours, and 5 (6.1%) patients in 11-15 hours. 44 (68.3%) patients in control group required up to 05 doses of analgesia after surgery. Twenty-six patients (31.7%) required six doses in control. While in bupivacaine instillation 50 patients (61%) required no analgesia. 19 (23.2%) patients required 1 dose of analgesia. 13 (15.9%) patients required 2 doses. No patient required more than two doses of analgesia in bupivacaine instillation group. Hence the number of doses of analgesia required by Control Group were 5.15 with a standard deviation of 0.72 minimum being 3 and maximum being 6. While a mean number of doses of analgesia required by Bupivacaine İnstillation group was 0.55 with standard deviation 0.76, the minimum requirement is 0 doses and a maximum of 2 doses. Mean time taken by patients in the control group to mobilize after surgery was noted to be 8.15 hours with a standard deviation of 1.78 while for bupivacaine instillation group to mobilize after surgery mean noted to be 5.02 hours with a standard deviation of 1.75. In the Control group, 10 (12.2%) patients were mobilized by 4 hours. 46 (56.1%) patients were mobilized in 8 hours, and 26 (31.7%) were mobilized at 10 h. In Bupivacaine instillation group, 61 (74.4%) patients were mobilized by 4 hours. 21 (25.6%) patients were mobilized in 8 h after surgery. In the control group, mean hospital stay noted was 36.97 hours with a standard deviation of 6.08; a minimum of 24 hours and a maximum of 48 h. While in bupivacaine instillation group, mean hospital stay noted was 25.9 hours with a standard deviation of 2.35; a minimum of 22 hours and a maximum of 32 h. In control group 62 (75.6%) patients took more than 30 hours till discharge from hospital and 17 (24.4%) were discharged within 30 h of admission. However, in Bupivacaine İnstillation Group, 79 (96.3%) were discharged within 30 h of admission, and 3.7% were discharged after 30 h.

Laparoscopic cholecystectomy is one of the most ordinary day-case surgeries ( 11 ). The post-operative pain associated with this minimally invasive procedure is generally less intense and lasts a shorter time than that follow open cholecystectomy but it remains prevalent the problem of the early post-operative period and may delay discharging patient, especially in day-case departments ( 12 ). The origin of pain after laparoscopic cholecystectomy is multi-factorial and is comprised of three different components: incisional pain (somatic), visceral pain, and shoulder pain (referred visceral pain). Pain after laparoscopic cholecystectomy demonstrates a high inter-individual variability in intensity as well as duration and is also mostly unpredictable (13). The intensity of pain is highest on the day of surgery and the following day, subsequently declining to low levels within 2-3 days and is most frequently reported at the site of incisions for trocar placement ( 14 ).

In the present study effectiveness of instillation of 0.25% bupivacaine at all three components contributing to post-op pain were infiltrated and it was found more effective than using at either site or none, as demonstrated in other studies ( 15 ). It significantly decreased the postoperative analgesia requirements, promoted early mobilization and therefore indirectly lead to significant benefits including reduced potential for deep vein thrombosis and pulmonary embolus, lesser incidence of atelectasis and respiratory infection, and minimal motor deconditioning.

Shorter hospital stays added to significance of using bupivacaine as an active practice in the number of prospects. Similar reports exist in the literature. A study conducted in the United Kingdom concluded that patients in the bupivacaine group had less pain in the early postoperative period and a lower incidence of pain in the right hypochondrium after instillation of Intraperitoneal bupivacaine ( 16 ). A randomized controlled trial conducted in Iran evaluated Postoperative pain, oral analgesic consumption, peak expiratory flow rate, and presence of nausea or vomiting was recorded at baseline and 4, 8, and 24 hours after surgery ( 17 ). Patients who received IP bupivacaine showed a significantly lower pain score and improved peak expiratory flow rate and received lower doses of ibuprofen within the first 24 hours after surgery. Likewise, the presence of nausea/vomiting was significantly lower in bupivacaine groups 1 and 4 hours after surgery. A Croatian study stated that pain was more intense in the saline group at each time point ( 15 ). Significant differences between the groups were present for up to 8h. Analgesic consumption was significantly lower in the bupivacaine group. No side-effects occurred. A study carried out in India also demonstrated that a moderate dose of intraperitoneal analgesia with a local anesthetic (ropivacaine and bupivacaine) is simple to use and effective method with minimal side effects ( 18 ). Use in the combination of the incision and intraperitoneal local anesthetic infiltration after Laparoscopic Cholecystectomy resulted in significantly reduced immediate postoperative pain and may explain the reduced use of analgesia and early discharge of patients ( 19 ). However, a randomized, placebo-controlled and double-blind study conducted in Sweden stated that intraperitoneal bupivacaine does not effectively reduce pain after laparoscopic cholecystectomy ( 20 ).

The sample size was small, and only those patients were recruited in the study who presented to Pakistan Insititute of Medical Sciences, Islamabad. Patients with cholelithiasis who did not come to this hospital were not inducted. This study was a comparative study, yet no effort was made to breakdown etiologic factors in both groups, and no analysis was therefore possible. Only two broad categories were defined: One, patients with cholelithiasis who underwent cholecystectomy followed by bupivacaine instillation and, two, those with cholelithiasis who underwent cholecystectomy followed by no intervention. Our data cannot be generalized at the national level. Though the outcome of instillation of bupivacaine is comparable with previous evidence, to address these shortcomings, we suggest that large scale, randomized trials be conducted to identify the possible difference in the outcome of bupivacaine instillation to reduce frequency of the analgesia demand by the patient, time to mobilize after surgery and post-op stay.

In future comparative trails of ropivacaine can be evaluated in comparison to bupivacaine as a drug for pain management after elective laparoscopic cholecystectomy. Ropivacaine is less lipophilic than bupivacaine and is less likely to penetrate large myelinated motor fibers, resulting in a relatively reduced motor blockade. The reduced lipophilicity is also associated with the decreased potential for central nervous system toxicity and cardio-toxicity as it is metabolized extensively in the liver and excreted in urine ( 21 ).

We have found that the instillation of bupivacaine is an effective method of providing adequate analgesia to the patient after elective laparoscopic cholecystectomy. All the cases were observed during their hospital stay until satisfactorily discharged from the hospital. It is mandatory to conduct large scale studies on this topic to validate the conclusions. We can suggest after laparoscopic cholecystectomy, on the final stage of closure, peritrocal site, sub-phrenic space and gallbladder bed instillation of bupivacaine (0.12%) can significantly reduce the frequency of the analgesia demand by the patient, time to mobilize after surgery and post-op hospital stay.