A Meta-Analysis of Randomized Controlled Trials Concerning the Efficacy of Transversus Abdominis Plane Block for Pain Control After Laparoscopic Cholecystectomy

Background and Purpose: Transverse abdominis plane (TAP) block has been suggested to reduce post-operative pain after laparoscopic cholecystectomy (LC). However, the literature is divided on whether ultrasound (USG)-guided TAP block is effective for pain control after LC. The present meta-analysis therefore evaluated the efficacy of USG-guided TAP block vs. controls and port site infiltration for pain control after LC. Methods: A comprehensive literature search of online academic databases was performed for published randomized controlled trials (RCTs) for studies published to January 31, 2021. The primary outcome analyzed was post-operative pain score at 0, 6, 12, and 24 h post-surgery, both during rest and while coughing. Secondary outcomes included morphine consumption and post-operative nausea and vomiting (PONV) incidence. Results: A total of 23 studies with data on 1,450 LC patients were included in our meta-analysis. A reduction in pain intensity at certain post-operative timepoints was observed for USG-guided TAP block patients compared to control group patients. No reduction in pain intensity was observed for patients receiving USG-guided TAP block patients vs. conventional Port site infiltration. Conclusion: This meta-analysis concludes that TAP block is more effective than a conventional pain control, but not significatively different from another local incisional pain control that is port site infiltration. Additional prospective randomized controlled trials are required to further validate our findings.


INTRODUCTION
Laparoscopic cholecystectomy (LC) is currently the gold standard treatment for symptomatic gall bladder disorders, including cholelithiasis and cholecystitis (1,2). However, LC, while minimally invasive, is associated with post-operative pain, especially within the first 24 h. This pain is routinely managed using opiates, which are associated with a number of side effects, including excessive sedation and post-operative nausea and vomiting (PONV). As these side effects may increase hospital stay durations, proper pain control and management are therefore critical for improving clinical outcomes and promoting earlier ambulation post-surgery (3)(4)(5).
Transversus abdominis plane (TAP) block is a regional anesthetic technique that has gradually become an alternative for post-operative pain control. It involves the infusion of local anesthetic into the fascial plane of the abdominal wall where the T6 to L1 nerves are found (5). Conventionally, TAP block was performed using anatomical landmarks, but ultrasound (USG)-guided TAP block has become more popular in recent years (6)(7)(8)(9)(10).
A previously published meta-analysis detailing seven randomized controlled trials (RCTs) showed TAP block to be effective when compared with standard analgesia in adults undergoing LC (11). However, they lacked evidence to compare the efficacy of TAP block against conventional port site infiltration for post-LC pain control. The current study aims to systematically review all available RCTs to evaluate the efficacy of USG-guided TAP block against conventional analgesia and port site infiltration in LC patients.

Search Strategy
This meta-analysis was performed using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines (12). A comprehensive literature search for RCTs published prior to January 31, 2021 was conducted using the following electronic databases: PubMed, Google scholar, Cochrane Library, Scopus, and TRIP. The following search terms were employed: "Transabdominal abdominis plane block" OR "Tap block" OR "Plane Block" OR "Ultrasound guided TAP block" AND "Laparoscopic cholecystectomy" AND "Pain Control" AND "Analgesic" OR "Local Anesthesia" OR "Infiltration anesthesia." Literature cited by included studies were also manually searched for additional eligible studies. The literature search did not restrict for language.

Study Eligibility Criteria
RCTs involving adult patients undergoing elective LC that compared the efficacy of USG-guided TAP block against either control or port-site infiltration groups were included. Studies that did not report pain outcomes were not included. Studies where full-texts were not available were not included.

Data Collection and Analysis
All eligible studies were screened by two independent reviewers using the selection criteria listed above. Screening first entailed abstract review, followed by full-text review. Any discrepancies were settled through discussion with a third reviewer. Articles published in a language other than English were machine translated using Google Translate and considered for inclusion. The following information was extracted from each included study: number of patients, investigation groups, types of analgesia used, outcome measurements, treatments, interventions, and adverse effects.

Primary Outcome
The primary outcome evaluated in this study was pain control in LC patients, as measured using 1-10 rating scales such as the visual analog scale (VAS) or numerical rating scale (NRS). Measurements at 0, 6, 12, and 24 h post-operation, both at rest and while coughing, were noted.

Secondary Outcomes
Secondary outcomes in this study included morphine consumption and post-operative nausea and vomiting (PONV) incidence.

Quality Assessment
Studies were assessed for quality using a modified JADAD score (13) that evaluated study methods, randomization approaches, blinding, withdrawals and dropouts, inclusion and exclusion criteria, approaches used to assess adverse effects, and statistical analysis. Scores ranged from 0 (lowest quality) to 8 (highest quality). Study quality was assessed independently by two reviewers. All discrepancies were resolved through discussion.

Publication Bias
Publication bias was assessed using funnel plot analysis. Funnel plot asymmetry was assessed using Egger's regression test (14,15).

Statistical Analysis
Mean difference (MDs) with 95% confidence intervals (CIs) was calculated for the continuous outcome. Risk ratios (RR) with 95% CIs were calculated for categorical outcomes to estimate pooled findings. Study heterogeneity was evaluated using the I 2 statistic. For I 2 values >50%, a random-effects model was applied. For I 2 values below 50%, a fixed-effect model was applied. Statistical analyses were conducted using Review Manager software (Version 5.3, Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration 2014).

Literature Search
Primary screening yielded 118 candidate articles. Of these, 47 underwent full-text screening and review. Ultimately, 23 studies containing data on 1,450 patients met inclusion criteria (Figure 1).

Characteristics of Included Studies
A full summary of extracted data from included studies is presented in Table 1. Included studies were published between 2009 and 2020, with individual study samples ranging from 40 to 120 individuals. All included studies were of moderate or high quality based on JADAD Score ( Table 2). Out of 23 included studies, 14 studies (16-18, 23-25, 27, 30, 31, 34-38, 40) were conducted in Caucasian individuals, with the remaining nine studies (19-22, 26, 28, 29, 32, 33) were conducted on an Asian population.

Post-operative Pain Intensity at Rest
Analysis of the included studies suggested significantly reduced pain intensity in patients receiving USG-guided TAP block relative to control group patients at 0, 6, 12, and 24 h postoperation (Figures 2A-D). However, no such reduction was noted when USG-guided TAP block patients were compared to Port site infiltration group patients ( Table 3). A high degree of heterogeneity was present in all included studies at all timepoints   # "1" means "Yes", "0" means "Not described".

Post-operative Pain Intensity While Coughing
A significant reduction in pain intensity while coughing was observed at 0, 6, and 24 h post-operation in USG-guided TAP block patients relative to control group patients (Figures 3A-D). No significant change in pain intensity was noted at 12 h postoperation. No significant changes were noted when comparing USG-guided TAP block patients to Port site infiltration group patients at all post-operative time-point ( Table 3).

DISCUSSION
This study evaluated the efficacy of USG guided TAP block for reducing pain intensity at rest and while coughing in LC patients for up to 24 h post-operation. We noted a significant reduction in pain intensity in patients who received USG-guided TAP block relative to control group patients, as well as reduced morphine consumption and incidence of PONV. However, no such reduction was noted when USG-guided TAP block patients were compared to Port site infiltration group patients at rest and during coughing at all post-operative timepoints upto 24 h.
Severe pain for LC patients generally occurs during the first 24 h post-surgery, and is thought to arise mainly from visceral tissue damage and the surgical incision (with the latter taking precedent) (41). As such, analgesic planning must focus on incisional pain rather than visceral pain. The absence of significant difference of pain control after port site infiltration    advocates too for an incisional pain control. Our results showed that USG-guided TAP block led to significantly reduced postoperative pain, as well as reduced morphine consumption and PONV incidence. These findings concur with a previous analysis of seven studies by Peng et al. (11). Recent RCTs have suggested that USG-guided TAP block plays an important role in multimodal pain therapy through proper visualization and improved accuracy. However, few studies have compared the effects of subcoastal TAP block with those of posterior TAP block. As such, our meta-analysis included RCTs that looked at both USG-guided TAP blocks and oblique subcostal TAP blocks. Nonetheless, we noted high heterogeneity between studies, suggesting that our meta-analysis results need to be treated with caution.
Our study has several limitations: (1) included studies had relatively small sample sizes; (2) extended follow-up data on chronic pain, long-term analgesic use, and adverse events was lacking; (3) multiple pain score scales were used; (4) a diverse range of anesthesia dosages were administered across the studies, and (5) insufficient study numbers for important factors such as laproscopic guided TAP block and fentanyl, tramadol, and opioid consumption, thereby precluding subgroup analysis.

CONCLUSION
This meta-analysis concludes that TAP block is more effective than a conventional pain control, but not significatively different from another local incisional pain control that is port site infiltration. Additional prospective randomized controlled trials are required to further validate our findings.

DATA AVAILABILITY STATEMENT
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

AUTHOR CONTRIBUTIONS
WW conceived and designed the study. WW and LW did literature search and analyzed the data. YG wrote the paper, reviewed, and edited the manuscript. All authors have read and approved the final manuscript.