Enhanced Recovery after Surgery (ERAS) is a systematic, evidence-based, multimodal approach to perioperative care designed to maximize the recovery of patients undergoing surgery. The ERAS program includes meticulously customized interventions and protocols tailored to specific surgical procedures, covering the preoperative, intraoperative, and postoperative stages1. Laparoscopic cholecystectomy has replaced open cholecystectomy as the treatment of choice for symptomatic gallstones and since it is minimally invasive is associated with less pain, less wound infections, reduced hospital stay, reduced morbidity and mortality and early return to work and improved overall quality of life. ERAS protocol is to improve surgical outcomes and ensure patient adherence through a holistic perioperative care strategy2. The key principles of the ERAS protocol include pre-operative counselling, preoperative nutrition, avoidance of perioperative fasting and carbohydrate loading up to 2 hours preoperatively, standardized anaesthesia and analgesic regimens (epidural and non-opioid analgesia) and early mobilization as follows3.

The gross difference between Enhanced Recovery after Surgery (ERAS) protocols and traditional protocols lies in their approach to perioperative care. ERAS protocols designed to optimize patient recovery, reduce complications, and shorten hospital stays4. This includes comprehensive preoperative education, minimal fasting, preoperative nutritional optimization, use of multimodal analgesia with minimal opioids, goal-directed fluid management, minimally invasive surgical techniques, early postoperative mobilization and early oral intake. In contrast, traditional protocols are often more rigid, often involve prolonged fasting, limited preoperative education, heavy reliance on opioids for pain management, routine rather than individualized fluid administration, open surgical techniques, delayed mobilization and feeding, and less coordinated multidisciplinary care, resulting in longer recovery times, higher complication rates, and lower patient satisfaction.

We conducted this prospective study with the aim to compare the efficacy of ERAS with traditional protocol in patients undergoing elective laparoscopic cholecystectomy. The primary objective of our study was to evaluate both protocols according to postoperative pain, postoperative events and length of stay and secondary objective was to compare the hemodynamic parameters and postoperative complications.

This randomized, prospective comparative study was conducted in a tertiary care teaching hospital from December 2022 to March 2024 after getting approval from the Institutional ethical committee (Human) and Clinical Trial Registry India registration number (CTRI/2024/02/062240). The research was performed according to the principles of the Declaration of Helsinki (2013). After obtaining written and informed consent from 60 patients of age 18-60 years of either sex belonging to American Society of Anaesthesiologist (ASA) Physical Status I/II/III posted for elective laparoscopic cholecystectomy under general anaesthesia. Patients with severe respiratory, cardiovascular or any other systemic disease, obese patients, pregnant patients, emergency surgeries, patients who need intraperitoneal drain, allergic reactions, patient refusal were excluded from the study.

In both groups, the patients underwent preoperative assessment, preoperative counselling about the procedure and the recovery period and preoperative optimisation of haemoglobin and associated mild to moderate systemic comorbidities. Intraoperatively optimal oxygen levels and maintaining normothermia and postoperatively analgesia and prophylaxis for postoperative nausea and vomiting (PONV) were followed in both the groups. Patients were divided in to two groups ERAS Group (Group E) (Patients with Enhanced Recovery After Surgery protocol), TRADITIONAL Group (Group T) Patients with the traditional method as per institutional protocol) with help of a computer-generated randomization list. Each participant was assigned a unique identification number. Sealed envelopes containing the allocation group are prepared according to the randomization list. Envelopes were only opened at the time of participant recruitment, ensuring that the researcher knew but the participant did not know the group assignment beforehand. The allocation process was conducted by an independent researcher who was not involved in participant recruitment or data collection, ensuring the concealment of group assignments from the study team.

ERAS group (E): patients received 100ml carbohydrate drink at 2 hours before on the day of surgery. Traditional group (T): Patients didn’t receive carbohydrate drink. Upon arrival in the operating room, a 20G peripheral intravenous cannula was secured, and standard ASA monitors (electrocardiography, non-invasive blood pressure, pulse oximetry, and capnography) with baseline parameters were recorded. Patients received preanesthetic medications with inj.Glycopyrrolate 0.2mg, inj.Tramadol 1mg/kg, and inj.dexamethasone 8mg intravenously. Preoxygenation with 100% oxygen was administered for 3 minutes. General anaesthesia was induced with inj.Sodium thiopentone 5-7mg/kg, inj.Succinycholine 2mg/kg and an appropriately sized cuffed endotracheal tube was inserted. Anaesthesia was maintained using controlled ventilation with sevoflurane (1.5%-2%) according to end stage gas analyser with an oxygen-nitrous oxide ratio of 50:50 and with inj atracurium 0.05mg/kg. All patients received postoperative analgesia inj Pcm 1g IV 20 minutes before extubation. Patients were reversed with Inj: Neostigmine 0.05mg/kg and Inj Glycopyrrolate 0.08mg/kg and after safe extubation shifted to postanaesthesia care unit (PACU) for observation. For prevention of PONV, inj.ondansetron 4mg was administered in both the groups in the postoperative period.

STUDY PROCEDURE

GROUP E (ERAS PROTOCOL):In this group according to the ERAS protocol, preoperative measures fasting protocol 6 hours before surgery solid food and 2 hours before surgery liquid intake (25% dextrose 100 ml) were administered and intraoperatively goal directed iv fluids given according to haemodynamic parameters, postoperatively breaking of fasting and early mobilization was advised.

Discharge Plan:

Patient were discharged once they fulfilled the following criteria:                                

Haemodynamically stable within 20% of preoperative vitals, ability to eat and drink, no nausea and vomiting, adequate pain control with oral analgesia, independently mobile without support, no complication requiring extended hospital care.

GROUP T (TRADITIONALGROUP)

 Patients included in this group received Standard /Traditional care. Preoperatively institutional fasting protocol were followed 8 hours before fatty meals, 6 hours before light meals, 2 hours before clear liquids. During intraoperative all patients received liberal iv fluids. Patients were started on oral feeding once bowel function was completely restored, defined by the presence of normal peristalsis, passage of flatus or depositions. Early mobilisation was done according to the attending surgeon decision.

Discharge Plan

Patients were discharged once a full normal diet was tolerated, achieved ambulation and pain was adequately controlled with oral analgesics.

The results from a randomized control study by Jun Li, et al.4 with an expected mean difference in duration of length of stay between the groups being1.92 and standard deviation of 5.91 and using the formula: n = 2(SD)2(Zα +Zβ)2/ d2 and confidence interval of 95% and power of the study is 80%, α error was allowed is 0.05. Z (1- α) is1.96 and Z (1-β) is 0.846. Data were reported as mean and standard deviation or median and interquartile range according to normality.

Statistical analysis were conducted using standard methods to assess the significance of difference between two groups ERAS group and traditional /conventional approach. Continuous variables such as age and Body Mass index (BMI) were presented as mean and standard deviation and analysed using Fisher exact test. Categorical variable including gender distribution were expressed as percentage and compared using Chi- square test. Primary outcomes such as length of hospital stay, early mobilisation, postoperative nausea and vomiting, postoperative analgesia, early oral intake were subjected to appropriate statistical tests. Chi square was applied for categorical outcomes while the Fisher exact for continuous variables. P value less than 0.05 was considered statistically significant.

Of the 80 patients assessed for eligibility 20 were excluded as they did not meet the inclusion criteria, and 4 declined to participate (consolidated standards of reporting trials (CONSORT) flow diagram of the study participants (figure 1). The 60 patients were randomised in to Group E and Group T.

Mobilization and independent mobilization showed a notable difference between the two groups. The Group E achieved both initial and independent mobilization earlier (median 8 hours) compared to the Group T (median 12 hours). While the difference in initial mobilization was not statistically significant (p=0.561), independent mobilization showed a significant difference (p=0.04). This suggests that the Group E may be more effective in promoting early patient mobility, which is a crucial factor in post-operative recovery.

Regarding the length of hospital stay, Group E had a median stay of 3days (IQR 1), while the Group T stayed for a median of 7 days (IQR 2). This difference reached statistical significance in this sample (p=0.051). Group E demonstrated remarkable effectiveness in preventing common post-operative complications, with no reported cases across all categories examined. In contrast,

the Group T experienced various complications, most notably in blood pressure regulation and glucose control. The most significant difference was observed in the incidence of hypotension/hypertension. While the Group E reported no cases, 46.6% of patients in the Group T experienced this complication showed highly statistically significant difference (χ2 = 18.261, p < 0.01). No cases of hyperglycaemia were reported in the Group E, compared to 20% in the Group T showing a statistically significant difference (Yates' χ2 = 10.63, p = 0.005). Throughout most of the 24-hour post-operative period, both groups show similar median VAS scores, predominantly at 2 hours.

The most notable differences were observed in blood pressure measurements. Systolic Blood Pressure (SBP): The Group E showed significantly lower SBP compared to the Group T (ERAS: median 120, IQR 11; Traditional: median 140, IQR 10; Z= -4.99, p<0.01), which depicts consistently lower SBP values for the Group E across all time points. Diastolic Blood Pressure (DBP), Similarly, the Group E demonstrated significantly lower DBP compared to the Group T (ERAS: median 78, IQR 10; Traditional: median 84, IQR 10; Z= -4.67, p<0.01), showing consistently lower DBP values for the Group E throughout the post-operative period.

TABLE 1: Comparison of baseline parameter between both the groups

(Table1: ASA: American Society of Anaesthesiology, SBP: Systolic Blood Pressure, DBP: Diastolic Blood Pressure, BMI: Body Mass Index, SD: Standard Deviation)

TABLE 2: POSTOPERATIVE VAS SCORE

TABLE 3: POSTOPERATIVE COMPLICATIONS

In both the groups (ERAS vs Traditional) there was no statistically significant difference found in patient demographics (age, sex, BMI, duration of surgery, ASA grade) and baseline characteristics [Table 1]. In our study pre-glucose levels in the Group E demonstrated statistically significant difference indicating that patients in the Group E had consistently lower baseline mean pre-glucose levels before the intervention. The Group E demonstrates a higher mean post-glucose level compared to the Group T. This difference is also statistically significant, suggesting that the Group E, which likely includes pre-operative carbohydrate loading, results in higher post-carbohydrate glucose levels. These glucose profile differences underscore the metabolic effects of the ERAS protocol compared to the Traditional method. Carbohydrates ultimately break down in to glucose which then serves as the primary metabolic fuel. After a carbohydrate drink, there is rise in blood glucose levels, which raises insulin secretion from the pancreas simultaneously. Insulin causes glucose to be deposited in the liver as glycogen, then during the next few hours, when blood glucose concentration falls, the liver releases glucose back in to the blood. Pia V Roder et al. 5also states that there will be rise in blood glucose after a meal. Mitsuhisa komatsu et al.6 conducted a study of glucose stimulated insulin secretion, in which he states that there will be rise in glucose level after a meal which stimulate beta cells of pancreas to release insulin. The higher post-carbohydrate RBS in the ERAS group is likely a direct result of the ERAS protocol's carbohydrate loading strategy. This approach aims to reduce insulin resistance and improve post-operative outcomes.

As in Figure (2,3,4) both systolic and diastolic blood pressures were statistically significant in the Group E compared Group T to at nearly all measured time points. The maintenance of stable haemodynamics in Group E aligns with the protocol's principles of minimizing the surgical stress response which may reflect reduced sympathetic activation and a more stable physiological state during surgery. Nanan Zhang et al.7 in their study showed that use of ERAS in perioperative period in patients reduces stress response.

The comparison of post-operative vitals between the Group E and the Group T reveals statistically significant differences in systolic and diastolic blood pressure. The significantly stable blood pressure in the Group E suggests that this protocol may be more effective in managing post-operative stress and pain. This could be attributed to various components of the ERAS protocol, such as improved pre-operative counselling, reducing patient anxiety, optimal fluid management during surgery, more effective pain management strategies, earlier mobilization and oral intake.

As per our study design, we used inj tramadol 1mg/kg iv as premedication and inj PCM 1 gm IV intraoperatively in both the groups. Throughout the 24-hour post-operative period, both groups show similar median VAS scores (Table 2). This suggests that both protocols maintained adequate pain control.

In this study there was marked reduction in postoperative complications in the Group E (Table3). Group E experienced no cases of postoperative hypotension/hypertension, hyperglycaemia, headache, or nausea/vomiting. Optimal fluid management8, goal directed fluid strategy, 250ml bolus and maintenance (1-2ml/kg IBW/hour) in Group E may help prevent fluid overload and associated complications such as carbohydrate loading9, Preoperative carbohydrate drinks, a common component of ERAS protocols, have been shown to reduce insulin resistance and improve glycaemic control. Early mobilization10: Rapid return to mobility can reduce the risk of thromboembolic events and improve cardiovascular stability, stress reduction11. The comprehensive approach of ERAS protocols, including patient education may reduce overall physiological stress and its associated complications12.

A key metric in evaluating the effectiveness of perioperative care protocols is the length of hospital stay (Figure 5). In this study, patients in the Group E had a median hospital stay of 3 days, compared to 7 days in the Group T. This potential reduction in hospital stay may lead to better patient outcomes and healthcare resource utilization. Patient benefits include shorter hospital stays are associated with reduced risk of hospital-acquired infections, faster return to normal activities, and improved patient satisfaction13. Healthcare system benefits include reduced length of stay can lead to significant cost savings and improved hospital bed capacity14. Praveen Kumar et al.15 (2024) showed reduced length of stay in his study. Earlier mobilization, faster return of bowel function, improved pain control, and reduced complications which play a role in facilitating earlier discharge. Ren L, Zhu D, Wei Y, et al. (2012)16 attenuates stress and accelerates recovery in patients after radical resection for colorectal cancer. The postoperative length of stay and expense for the ERAS group were reduced in comparison to the controls. Dhiman AK et al. (2022)17 found out hospital stay was significantly shorter in the ERAS group: 4.67 days verses 13.36 days.

One of the key principles of ERAS protocols is early mobilization after surgery, and the results of this study strongly support the effectiveness of this approach. Patients in the Group E achieved independent mobilization significantly earlier than those in the traditional group (median 8 hours vs 12 hours). This earlier mobilization is associated with numerous benefits including reduced risk of thromboembolic events, faster return of bowel function, and overall improved recovery18. The ability to achieve earlier mobilization in the Group E is due to optimized pain management, minimized use of drains and catheters18, reducing the use of invasive devices can make it easier for patients to move comfortably, Early oral intake18,allowing patients to eat and drink sooner after surgery can improve energy levels and facilitate mobility, Patient education include preoperative counselling in ERAS protocols often emphasizes the importance of early mobilization, potentially improving patient engagement and compliance. Praveen et al.15also found a statistically lesser time needed for the first mobilization in the ERAS group compared to the standard hospital care protocol. Lester et al.19in 2018 also concluded that mean post-operative ambulation time was 9.6 hours in ERAS group compared to 32.89 hours in pre-ERAS groups respectively

The present prospective study offers a strong evaluation of ERAS protocol in laparoscopic cholecystectomy. Reduced length of hospital stays, early mobilization, reduced postoperative complications and events contribute to the strength of our study.

Limitations of the study are that our study was at a single instituition with smaller sample size and also only laparoscopic cholecystectomy as the surgical procedure was included in our study. We could not follow the opioid free anaesthesia protocol and multi-modal analgesia regimen in our study. We could not study the patient satisfaction, recovery experience and the functional status of the patient for long term follow up. Also, ours being government setup we could not analyse the impact of cost effectiveness of our study on health care system. Further research should be conducted for larger sample size at multiple institutions for implementation of procedure specific ERAS protocols for optimising outcomes especially in high-risk patient population undergoing extensive laparoscopic procedures.

This study demonstrated several benefits of the ERAS protocol in laparoscopic cholecystectomy including earlier mobilization, and reduced length of stay, stable perioperative hemodynamics and lesser incidence of postoperative complications. This study also provided strong support for the potential advantages of ERAS protocols in laparoscopic cholecystectomy suggesting improved patient outcomes and potentially shorter hospital stays without compromising pain control as evidenced by similar pain scores and need of rescue analgesia between both the groups.

1. Brown JK, Singh K, Dumitru R, Chan E, Kim MP. The Benefits of Enhanced Recovery After Surgery Programs and Their Application in Cardiothoracic Surgery. Methodist DeBakey Cardiovasc J. 2018;14(2):77–88.
2. Weimann A. Is there a rationale for perioperative nutrition therapy in the times of ERAS? Innov Surg Sci. 2019 Nov 30;4(4):152–7.
3. Weimann A, Braga M, Harsanyi L, Laviano A, Ljungqvist O, Soeters P, et al. ESPEN Guidelines on Enteral Nutrition: Surgery including organ transplantation. Clin Nutr Edinb Scotl. 2006 Apr;25(2):224–44.
4. Li J, Li H, Xv ZK, Wang J, Yu QF, Chen G, et al. Enhanced recovery care versus traditional care following laminoplasty: A retrospective case-cohort study. Medicine (Baltimore). 2018 Nov;97(48)e13195.
5. Röder PV, Wu B, Liu Y, Han W. Pancreatic regulation of glucose homeostasis. Exp Mol Med [Internet]. 2016 Mar [cited 2024 Sep 5];48(3)e219–e219. Available from: https://www.nature.com/articles/emm20166.
6. Augmentation of Insulin Release by Glucose in the Absence of Extracellular Ca2+: New Insights Into Stimulus-Secretion Coupling | Diabetes | American Diabetes Association [Internet]. [cited 2024 Sep 5]. Available from: https://diabetesjournals.org/diabetes/article/46/12/1928/10127/Augmentation-of-Insulin-Release-by-Glucose-in-the
7. Lu Q, Zhang N, Wang F, Chen X, Chen Z. Surgical and oncological outcomes after laparoscopic vs. open major hepatectomy for hepatocellular carcinoma: a systematic review and meta-analysis. Transl Cancer Res [Internet]. 2020 May [cited 2024 Aug 28];9(5):3324–38. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798952/
8. Correa-Gallego C, Tan KS, Arslan-Carlon V, Gonen M, Denis SC, Langdon-Embry L, et al. Goal-Directed Fluid Therapy using Stroke Volume Variation for Resuscitation after Low Central Venous Pressure Assisted Liver Resection. A Randomized Clinical Trial. J Am Coll Surg. 2015 Aug;221(2):591–601.
9. Kendrick JB, Kaye AD, Tong Y, Belani K, Urman RD, Hoffman C, et al. Goal-directed fluid therapy in the perioperative setting. J Anaesthesiol Clin Pharmacol. 2019 Apr;35(Suppl 1):S29–34.
10. Tong E, Chen Y, Ren Y, Zhou Y, Di C, Zhou Y, et al. Effects of preoperative carbohydrate loading on recovery after elective surgery: A systematic review and Bayesian network meta-analysis of randomized controlled trials. Front Nutr [Internet]. 2022 Nov 23 [cited 2024 Sep 6];9.Availablefrom:https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.951676/full
11. Rn) OR for N (Open, Ernstmeyer K, Christman E. Chapter 13 Mobility. In: Nursing Fundamentals [Internet] [Internet]. Chippewa Valley Technical College; 2021 [cited 2024 Sep 6]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK591828/
12. Cardiovascular Deconditioning - an overview | ScienceDirect Topics [Internet]. [cited 2024 Sep6].Availablefrom:https://www.sciencedirect.com/topics/nursing-and-health-professions/cardiovascular-deconditioning
13. Ata A, Lee J, Bestle SL, Desemone J, Stain SC. Postoperative hyperglycemia and surgical site infection in general surgery patients. Arch Surg Chic Ill 1960. 2010 Sep;145(9):858–64.
14. Zhang N, Wu G, Zhou Y, Liao Z, Guo J, Liu Y, et al. Use of Enhanced Recovery After Surgery (ERAS) in Laparoscopic Cholecystectomy (LC) Combined with Laparoscopic Common Bile Duct Exploration (LCBDE): A Cohort Study. Med Sci Monit Int Med J Exp Clin Res [Internet]. 2020 Sep 12 [cited 2024 Sep 5];26:e924946-1-e924946-6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510172/
15. B Praveen kumar, S Vinoth kumar,S Senthil Sudarsan, CP Ganesh Babu. Comparison of enhanced recovery after surgery(ERAS) protocol versus Conventional Approach for Laparoscopic Cholecystectomy: An Interventional Study. Available from www.jcdr.net.com.
16. Ren L, Zhu D, Wei Y, Pan X, Liang L, Xu J, et al. Enhanced Recovery After Surgery (ERAS) Program Attenuates Stress and Accelerates Recovery in Patients After Radical Resection for Colorectal Cancer: A Prospective Randomized Controlled Trial. World J Surg [Internet]. 2012 [cited 2024 Aug 28];36(2):1. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1007/s00268-011-1348-4
17. Dhiman AK, Jagne N, Uniyal M, Kumar A, Azam Q. Enhanced recovery after surgery protocol versus conventional care in emergency abdominal trauma surgery: a prospective, randomised, controlled study. Int Surg J [Internet]. 2022 [cited 2024 Sep 5];9(1):118–23. Available from: https://www.ijsurgery.com/index.php/isj/article/view/8326
18. Mithany RH, Daniel N, Shahid MH, Aslam S, Abdelmaseeh M, Gerges F, et al. Revolutionizing Surgical Care: The Power of Enhanced Recovery After Surgery (ERAS). Cureus. 15(11):e48795
19. Lester SA, Kim B, Tubinis MD, Morgan C, Powell MF. Impact of an enhanced recovery program for cesarean delivery on postoperative opioid use. Int J Obstet Anesth. 2020 Jan 22;43.