Propensity score-matched comparison of safety outcomes between high-risk and low-risk patients towards early hospital discharge after laparoscopic cholecystectomy

Background: Laparoscopic cholecystectomy (LC), a common treatment for symptomatic gallstones, has demonstrated safety in low-risk patients. However, existing data are scarce regarding the safety of LC in high-risk patients and the feasibility of early hospital discharge. Materials and methods: This retrospective study included 2296 patients diagnosed with symptomatic gallstones who underwent LC at a tertiary care centre from January 2009 through December 2019. The authors employed propensity score matching to mitigate bias between groups. Statistical significance was set at P less than 0.05. Results: The median age of the patients was 56 years (range 46–67), with a mean BMI of 25.2±4.3 kg/m2. Patients were classified as: American Society of Anesthesiologists (ASA) I (19.7%), II (68.3%), III (12.0%), and IV (0%). ASA I–II included low surgical risk patients (88%) and ASA III–IV comprised high-risk patients (12%). The LC-related 30-day reoperative rate was 0.2% and the readmission rate was 0.87%. Nine patients (0.4%) sustained major bile duct injuries, resulting in a conversion rate of 2.4%. The postoperative mortality rate was 0.04%, and the mean hospitalization time was 3.5 days. Patients in the high-risk group with a history of acute cholecystitis exhibited greater estimated blood loss, longer operative times, and were significantly more likely to be in the longer-stay group. Conclusion: These findings suggest that LC can be conducted safely on high-risk patients, and early hospital discharge is achievable. However, specific factors, such as a history of acute cholecystitis, may result in prolonged hospitalization owing to increased blood loss and longer operative times.

Ambulatory LC has been proven safe and cost-effective since the early 1990s [7,8] .but its acceptance, especially in developing countries, has been limited due to concerns about postoperative complications [9,10] .Therefore, establishing principles for optimizing ambulatory procedures is essential for success and patient safety.Although the safety and feasibility of ambulatory LC have been reported for low-risk and high-risk patients [11][12][13][14][15] , there is a lack of studies specifically focusing on high-risk patients.Ambulatory LC remains uncommon for patients classified as American Society of Anesthesiologists (ASA) grade III.
In Thailand, since 2018, public hospitals have implemented 1day surgery programs, including ambulatory LC, supported by the government [16] .This policy aims to enhance patient recovery, satisfaction, and cost-effectiveness by allowing suitable patients

HIGHLIGHTS
• This retrospective study included 2296 patients with symptomatic gallstones who underwent laparoscopic cholecystectomy (LC) at a tertiary care centre between 2009 and 2019.• LC was found to be safe in both low-and high-risk patients, with low 30-day reoperation (0.2%) and readmission rates (0.87%).• Early hospital discharge is feasible for high-risk patients undergoing LC and cost-effective.• Factors such as a history of acute cholecystitis may result in longer hospitalizations.
to be discharged within 6 h [17,18] .However, careful patient selection is crucial for ambulatory LC, and its feasibility in highrisk patients has been inadequately explored [14,15] .Our study aims to report the experience of LC in a tertiary hospital, compare postoperative outcomes between high-risk and low-risk patients, and evaluate safety outcomes in early vs. late discharge groups among high-risk patients.

Research question and aims
The main focus of our study was threefold: Firstly, to provide a comprehensive overview of the LC experience within a tertiary hospital setting.Secondly, to conduct a propensity score comparison of postoperative outcomes between high-risk and lowrisk patients who underwent LC.And finally, to assess the safety outcomes associated with early and late discharge within the high-risk patient group.

Data collection
Retrospective data were collected from gallstone-related symptom patients who underwent LC at a tertiary care hospital between January 2009 and December 2019.Exclusions included patients undergoing concurrent procedures, double gallbladder anatomy, or diagnosed with gallbladder cancer.Patient characteristics, laboratory results, preoperative ultrasonography findings, and surgical techniques were reviewed.Intraoperative and postoperative complications were classified using the Clavien-Dindo system.High-risk patients were defined as ASA greater than 2, while low-risk patients were ASA less than or equal to 2. Early discharge was defined as within 24 h postoperatively, and late discharge as after 24 h.LC procedures mainly used the conventional or alternative fundus-down technique based on surgeon judgment.Standard four-port approach with a 30°laparoscope was employed.Pneumoperitoneum was achieved using an open technique, maintaining intra-abdominal pressure at 12-15 mmHg.Postoperatively, patients were given a liquid or soft diet and discharged within one to 2 days.Follow-up appointments were recommended within 2 weeks or sooner for complications such as infection, abdominal pain, jaundice, or fever.Port-site hernia detection occurred during routine follow-up.

Ethical approval
This study was approved by our Research Ethics Committee.The study design, data collection methods, and informed consent procedures were reviewed and approved by the committee.The study was conducted in accordance with the principles outlined in the Declaration of Helsinki and adhered to relevant national and institutional guidelines.Given the retrospective nature of our study, the need for informed consent was waived.

Statistical analysis
Statistical analyses were conducted using R software version 4.1.1 [19].
The infundibular approach was performed in 1624 patients (70.7%) and required the fundus-down technique in 673 patients (29.3%).The mean operative time was 131.7 47.6 minutes, and the mean hospital stay was 2.4 2.7 days.Major and minor bile duct injuries occurred in nine (0.4%) and 22 (0.9%) patients, respectively.Conversion from laparoscopy to open cholecystectomy was performed in 54 patients (2.4%).The causes for conversion were due to severe adhesions, bleeding, bile duct injury, and uncertain cystic duct stump closure in 44, 5, 3, and 2 patients, respectively.Postoperative mortality occurred in one patient (0.04%).Within 30 days, four patients (0.2%) required reoperation, and the LC-related 30-day readmission rate was 0.87%.The median follow-up time in this study was 24 days (range 14-131).During the follow-up period, 55 patients (2.4%) developed surgical site infections (which) treated with antibiotics.Trocar site hernia (TSH) was detected at the umbilical port site in 13 patients (0.6%).Other complications according to the Clavien-Dindo classification are shown in Supplement 1, Supplemental Digital Content 1, http://links.lww.com/MS9/A251.
Table 1 shows the comparison of patient characteristics according to the ASA classification between low-risk (ASA ≤ 2) and high-risk (ASA > 2) patients categorized by unmatched and matched data.The operative outcomes of the 276 matched patients in each group were compared.Only the higher estimated blood loss in the high-risk group was statistically significant (10 vs. 5 ml; P = 0.005).The length of hospital stay between the two groups was slightly different but not statistically significant (Table 2).
Table 3 shows patient characteristics and operative results in the high-risk patient group divided into early and late hospital discharge.Patient characteristics including age, sex, BMI, and comorbidities between the two groups were not statistically different.However, patients with a history of acute cholecystitis detected from imaging or intraoperative findings, or multiple episodes of biliary colic required a longer hospital stays.Furthermore, patients experiencing a greater volume of estimated blood loss and a longer operative time were significantly more likely to be in the longer-stay group.

Discussion
The reported incidence of major bile duct injuries ranges from 0.02 to 1.5% [20][21][22][23] .In this study, nine (0.4%) patients had major bile duct injuries, a rate consistent with other studies.Four patients underwent ERCP and stent insertion, three underwent suture repair, and two required hepaticojejunostomy reconstruction.Severe adhesions were a common operative finding in these cases.Minor bile duct injuries occurred in 22 (0.9%) patients, managed with either endoscopic stent insertion or surgical repair.These patients performed well during follow-up.Significant vascular injuries, with a reported incidence of 0.03-0.06%,are the second most common cause of death after anaesthesia-related complications in patients undergoing LC [24] .However, none of the patients in this study had a significant vascular injury.The incidence of conversion to open surgery has been reported to range from 2.6 to 7.7% [1,25,26] ; however, the conversion rate in this study was slightly lower at 2.4%, with severe adhesion as the primary reason.Reoperation within 30 days was necessary in four patients due to various complications: (i) bleeding from the gallbladder bed on day 0, (ii) hepatic flexure colon injury on day 1, (iii) ileal injury on day 2, and (iv) total transection of the common hepatic duct on day 10.One of the four patients developed cardiac arrest 6 h postoperation.The patient underwent reoperation after successful cardiopulmonary resuscitation and bleeding from the gallbladder bed was detected.Bleeding was stopped using multiple haemostatic techniques, including abdominal packing.However, the patient later died of multiorgan failure.This represents the only death (mortality rate 0.04%) in our study, compared to other studies where the mortality rates following LC ranged from 0.15% to 0.5% [27,28] .Twenty patients (0.87%) had LC-related readmissions within 30 days, which was quite low.A meta-analysis by McIntyre et al. [29] reported an overall readmission rate of 3.3% (range 0.0-11.7%).In our study, 55 patients (2.4%) developed surgical site infection (SSI) but were all successfully treated with antibiotics and wound care.[32] , emphasizing that SSI should be considered as a predisposing factor for TSH [33,34] .The incidence of TSH has been reported to be 0.2-1.7% [3,33,35].Our study detected TSH in 13 patients (0.6%), a rate within the reported range.However, these hernias were located at the umbilical site, which differs from some studies reporting hernias at various sites, including the umbilical port, epigastrium, and right upper quadrant [3,33] .
A comparison of LC safety between low-and high-risk patients revealed a low incidence of LC-related complications in both groups.This study showed that the overall complication rate, operative time, conversion to open surgery, 30-day reoperation rate, and 30-day readmission rate were not significantly different between the groups.Although the median estimated blood loss was statistically significantly greater in the high-risk group, the difference was only 5 ml (10 vs. 5 ml), which is not clinically important.Comparative studies between different risk groups for non-ambulatory LC are relatively scarce, given the established safety of LC, as evidenced by a 30-year systematic review by Pucher et al.They reported a minimal morbidity range of 1.6-5.3%,mortality of 0.08-0.14%,and conversion rates between 4.2 and 6.2% [23] .Musbahi et al. found that the most common negative outcome in high-risk cases was readmission, occurring in 23 (9.43%) patients, while mortality was least common, occurring in two (0.82%) patients [5] .
When comparing the early and late discharge groups in the high-risk patient group, the percentage of overall complications in the late discharge group was more than twice that in the early discharge group (19.3% vs. 8.7%; P = 0.062).This was most likely because a greater percentage of patients in the late discharge group had a history of acute cholecystitis (31.4% vs. 11.6%;P = 0.002), acute cholecystitis based on imaging studies or intraoperative findings (23.7% vs. 8.7%; P = 0.012), or  b No complication in Clavien-Dindo classification grade V. c A number of cases were not successfully matched during the propensity score matching process, leading to their exclusion from the subsequent analysis.Data are presented as n (%) unless otherwise indicated.CBD, common bile duct; LC, laparoscopic cholecystectomy.
multiple episodes of biliary colic (98.6% vs. 92.8%;P = 0.025).Therefore, the operative time was significantly longer (145 vs. 115 min, P < 0.001).Although complications from LC can impact the duration of hospital stay, operative time has been identified as a predictor or influential factor on postoperative hospital stay after LC [12,36,37] .Moreover, patients with a history of acute cholecystitis, cholangitis, or pancreatitis and patients with an abdominal drain or pain score greater than 3, severe postoperative pain, or postoperative nausea and vomiting had a longer hospital stay [37,38] .Despite differences in LC complications between the groups, there was no significant difference in complication rate, conversion to open surgery, 30-day reoperation, and 30-day readmission rates in this study.Furthermore, the slightly greater estimated blood loss (10 vs. 5 ml; P < 0.001) in the high-risk group was not statistically significant.Previous studies align with our findings, reporting safety outcomes in ambulatory LC for both low-risk [11][12][13] and high-risk patients [14,15] .This suggests that the duration of hospital stay can be reduced while maintaining safety standards in high-risk patients, thereby highlighting the potential for early discharge post-LC.To achieve early discharge, implementation of a cholecystectomy surgery protocol designed for enhanced recovery, as suggested by a systematic review by Cole [39] could be beneficial.Such a protocol could decrease the recovery time and hospital stay length for patients undergoing LC, thus improving day-case surgery success rates.Our results on LC safety outcomes in high-risk and lowrisk patients provide compelling evidence to establish safe early discharge protocols in patients with LC to reduce hospital crowding, healthcare workload, overall costs, and patient stress [17] .Furthermore, a study on the financial benefits of an ambulatory program reported savings exceeding 300% per year [40] .

Strengths and limitations
This study's strengths include a large patient cohort from a single tertiary care hospital and the use of propensity score-matched analysis to balance variables and reduce bias.Limitations include the focus on surgical complications and the exclusion of other complications (e.g.pain, nausea/vomiting, abdominal drains) due to the retrospective design.One patient, who had intended to undergo a LC, needed to terminate the procedure immediately upon entry into the abdomen due to vascular injury.However, since no LC-related operation had been initiated, this patient was also excluded from the study.
An important limitation of this study is that the analysis did not encompass the causes of late discharge among the cohort of 276 high-risk patients.As a result, the potential factors contributing to the late discharge were not thoroughly explored within the scope of this research.This limitation could influence a comprehensive understanding of the discharge process and its associated challenges in this specific population.
Missing data are the potential limitations as some patients sought care elsewhere before routine follow-up.Additionally, the sample size of the high-risk group may limit robust conclusions (1 − β = 0.604).Future studies should include a larger number of high-risk patients for more definitive results.

Conclusion
In conclusion, it is safe to perform LC in high-risk patients and discharge them early from the hospital.Nevertheless, a history of acute cholecystitis can prolong hospital stays due to longer operative times and increased estimated blood loss.

Table 2
Comparison of operative and postoperative outcomes in the lowrisk and high-risk groups in a propensity score-matched patient population

Table 3
Patient characteristics and operative results of high-risk patients with early and late hospital discharge a .

Table 3 (
Continued) a Early and late hospital discharges were defined as discharge before and 24 h postoperatively, respectively.b No complication in Clavien-Dindo classification grade II, V. c A number of cases were not successfully matched during the propensity score matching process, leading to their exclusion from the subsequent analysis.Data are presented as n (%) unless otherwise indicated.ALP, alkaline phosphatase; BT, body temperature; CBD, common bile duct; ERCP, endoscopic retrograde cholangiopancreatography; IHD, intrahepatic duct; LC, laparoscopic cholecystectomy; SGOT, serum glutamate oxaloacetate transaminase; SGPT, serum glutamate pyruvate transaminase; WBC, white blood cell.