Abstract
Objective This study explored the efficacy of paracetamol mannitol injection combined with TAPB for postoperative pain relief in elderly patients after laparoscopic radical gastrectomy, as this combined regimen also reduces postoperative complications including delirium, nausea, vomiting and impaired wound healing, offering a novel strategy for postoperative pain management in such patients. Methods This prospective study included 150 elderly patients (≥65 years) undergoing laparoscopic radical gastrectomy, who were randomly assigned to three groups: sufentanil alone (S), sufentanil plus TAPB (ST), and sufentanil combined with TAPB and paracetamol mannitol (STA). All patients received routine vital sign and BIS monitoring with standardized vascular access establishment before anesthesia. Each group received corresponding preoperative interventions, and multiple perioperative indicators were compared, including opioid consumption, hemodynamic parameters, surgical and anesthetic variables, postoperative pain scores, adverse events, recovery outcomes and patient satisfaction. Results No significant intergroup differences were found in baseline demographics, perioperative indicators, intraoperative vital signs, vasoactive agent use, postoperative adverse reactions, gastrointestinal recovery indicators and bile acid levels among the three groups (all P>0.05). Compared with Group S and ST, the STA group presented decreased intraoperative consumption of sufentanil, remifentanil and propofol, reduced postoperative morphine requirement, prolonged time to the first moderate-severe pain, lower postoperative visual analogue scale (VAS) pain scores, higher early postoperative Confusion Assessment Method (CAM) scores without postoperative delirium, superior patient satisfaction, milder shoulder pain, earlier out-of-bed activity and shorter hospital stay; additionally, the ST group consumed fewer intraoperative anesthetics and exhibited better analgesic effects than the S group, while the slight difference in morphine consumption between the STA and ST groups was not statistically significant. Conclusions Combined application of TAPB and paracetamol mannitol can effectively alleviate early postoperative pain, cut down opioid consumption, relieve pain-induced restrictions on out-of-bed activity and improve satisfaction in elderly patients undergoing laparoscopic radical gastrectomy, which greatly optimizes postoperative pain management; meanwhile, paracetamol mannitol brings no extra risks to gastrointestinal function recovery or gastrointestinal bleeding, ensuring its safe application for postoperative analgesia in this elderly patient population.
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Published in
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Journal of Surgery (Volume 14, Issue 3)
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DOI
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10.11648/j.js.20261403.11
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Page(s)
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39-48 |
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Creative Commons
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This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
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Copyright
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Copyright © The Author(s), 2026. Published by Science Publishing Group
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Keywords
Paracetamol Mannitol, Transversus Abdominis Plane Block (TAPB), Gastric Carcinoma, Multimodal Pain Management, Postoperative Delirium (POD)
1. Introduction
Gastric cancer is a common malignant digestive tumor, with 1.09 million new cases and 770,000 deaths worldwide in 2020
| [1] | Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May; 71(3): 209-249. https://doi.org/10.3322/caac.21660 Epub 2021 Feb 4. |
[1]
. Laparoscopic radical gastrectomy causes severe postoperative pain due to extensive surgical trauma and physiological structural changes. Insufficient pain control contributes to multiple complications including cognitive dysfunction, cardiovascular events and delayed wound healing, and may further develop into chronic pain
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https://doi.org/10.1080/14737175.2023.2284872 Epub 2023 Dec 15. |
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[2, 3]
. With population aging, the number of elderly patients undergoing abdominal surgery continues to rise, accompanied by higher risks of postoperative complications and mortality
| [1] | Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May; 71(3): 209-249. https://doi.org/10.3322/caac.21660 Epub 2021 Feb 4. |
| [4] | E i uchinaka, takehiko hanaki, masaki morimoto, et al. the barthel index for predicting postoperative complications in elderly patients undergoing abdominal surgery: a prospective single-center study [j]. in vivo, 2022, 36(6): 2973-2980.
https://doi.org/10.21873/invivo.13041 |
[1, 4]
. Postoperative resting pain is an independent risk factor for postoperative delirium (POD), and persistent pain greatly increases delirium risk, severely hindering the recovery of elderly patients
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[5]
.
Conventional postoperative analgesia mainly relies on opioids, which frequently induce opioid-related adverse events (ORAE) such as nausea and respiratory depression, prolong hospital stay and increase medical costs
| [6] | Frances e lennon, tamara mirzapoiazova, bolot mambetsariev, et al. overexpression of the μ-opioid receptor in human non-small cell lung cancer promotes akt and mtor activation, tumor growth, and metastasis [j]. anesthesiology, 2022, 116(4): 857- 867. https://doi.org/10.1097/ALN.0b013e31824babe2 |
| [7] | He zj, xie kj, huang zx, et al. effect of low-opioid regimens on the incidence of postoperative delirium in elderly patients with gastric cancer surgery [j]. national medical journal of china, 2022, 102(05): 326-331. |
[6, 7]
, while impairing immunity and promoting tumor progression. Multimodal analgesia exerts synergistic effects via multiple targets to reduce drug dosage and adverse reactions
| [8] | Professional committee of oncologic anesthesia and analgesia, china anti-cancer association. chinese expert consensus on perioperative pain management in cancer patients (2020 edition) [j]. chinese journal of clinical oncology, 2020, 47(14): 703-710. |
[8]
. Ultrasound-guided transversus abdominis plane block (TAPB) is widely applied in abdominal surgery, yet it cannot effectively relieve resting pain and shoulder pain, resulting in excessive opioid consumption
| [9] | Miao zhu, wenchao sun. analgesic effects of ropivacaine combined with dexmedetomidine in transversus abdominis plane block in patients undergoing laparoscopic cholecystectomy: a systematic review and meta-analysis [j]. j perianesth nurs, 2023 jun, 38(3), 493–503.
https://doi.org/10.1016/j.jopan.2022.09.003 |
[9]
.
As a first-line agent for acute pain in the elderly, paracetamol presents favorable safety without gastrointestinal damage or respiratory depression, and its analgesic mechanism is mediated by endogenous cannabinoid pathways
| [10] | Christophe mallet, jules desmeules, rassa pegahi, et al. an updated review on the metabolite (am404)-mediated central mechanism of action of paracetamol (acetaminophen): experimental evidence and potential clinical impact [j]. j pain res, 2023, 29, 16: 1081-1094.
https://doi.org/10.2147/JPR.S393809 |
| [11] | Li jj, zhao m, fu yq, et al. research progress on preoperative frailty and risk of postoperative delirium in elderly patients [j]. practical geriatrics, 2023, 37(09): 951-955. |
[10, 11]
. The domestic paracetamol mannitol injection can additionally alleviate pneumoperitoneum-related injury and incision edema, and it is recommended for elderly opioid-sparing analgesia in clinical consensus. This prospective randomized controlled trial aimed to explore the clinical efficacy of TAPB combined with paracetamol mannitol injection in elderly patients undergoing laparoscopic gastrectomy, and to analyze its effects on postoperative pain, opioid consumption and POD incidence, so as to provide evidence for optimized perioperative analgesia and enhanced recovery.
2. Materials and Methods
2.1. Study Design
This study was a prospective randomized controlled trial. Elderly patients scheduled for elective laparoscopic multi-port radical gastrectomy were enrolled and randomly divided into three groups at a 1: 1: 1 ratio to compare the efficacy of different analgesic regimens. A total of 150 eligible elderly patients received interventions based on group allocation, with 48-hour postoperative morphine rescue consumption recorded as a core indicator. Postoperative delirium incidence was assessed at 2 h, 6 h, day 1, day 2 and day 3 after surgery. Intraoperative anesthetic dosage, extubation time and vital signs were continuously monitored. Postoperative VAS pain scores were measured at multiple time points. Perioperative dynamic changes in bile acids, gastrointestinal function recovery indicators and 48-hour postoperative complications were also documented.
2.2. Grouping and Interventions
From Dec 2023 to Jun 2024, 150 elderly patients awaiting laparoscopic gastrectomy were screened. After signing anesthesia informed consent, 150 qualified participants were assigned serial numbers and randomly divided via a random number table into three groups (50 cases per group): sufentanil group (Group S), sufentanil combined with TAPB group (Group ST), and sufentanil + TAPB + paracetamol mannitol group (Group STA). Thirty minutes before anesthesia induction, Group STA received ultrasound-guided subcostal TAPB combined with intravenous 1 g (100 mL) paracetamol mannitol injection. Group ST underwent identical TAPB and received 100 mL of 0.9% normal saline intravenously. Group S was administered only 100 mL of 0.9% normal saline without nerve block.
2.3. Blinding Design
All patients were informed of alternative postoperative analgesia protocols with specific group allocation concealed. Uniform ultrasound operation procedures were applied in Groups ST and STA to ensure patients were unaware of additional drug administration. Sham abdominal disinfection was performed in Group S to maintain blinding. Postoperative VAS scoring, CAM delirium evaluation and statistical analysis were completed by independent researchers blinded to group assignments.
2.4. Anesthesia Management
2.4.1. Preoperative Preparation
Anesthesia machines, monitors and infusion pumps were fully inspected for normal operation, with breathing circuits and connecting parts strictly checked for air leakage. Soda lime absorbers were examined to prevent carbon dioxide reabsorption. Essential supplies, including laryngoscopes, tracheal tubes and arterial puncture kits, were prepared in advance. All patients fasted for over 8 hours and abstained from drinking for 2 hours preoperatively. Routine monitoring covered SpO2, NIBP, lead II ECG, respiratory rate and BIS. After a positive Allen test, left radial artery puncture and catheterization were performed under local anesthesia for continuous invasive arterial blood pressure monitoring. Pressure transducers were zeroed at the standard position before formal monitoring. The preoperative interventions for the three groups were implemented uniformly 30 minutes prior to anesthesia induction.
2.4.2. TAPB Procedure
All ultrasound-guided TAPB procedures were performed by experienced anesthesiologists under sterile conditions via a subcostal approach in the supine position. A linear ultrasound probe was placed to visualize the rectus abdominis, oblique abdominal muscles and transversus abdominis layer. Real-time scanning clearly displayed the hierarchical structure of the abdominal wall. An in-plane needle insertion technique was adopted. Normal saline (1–2 mL) was injected for hydrodissection to confirm the correct fascial plane between internal oblique and transversus abdominis muscles. A total of 30 mL of 0.33% ropivacaine was injected gradually under real-time ultrasound guidance to achieve adequate drug diffusion in the target fascia. Contralateral TAPB was completed with the same method. Successful block was confirmed by decreased pinprick sensation in the surgical area.
2.4.3. Anesthesia Induction
Anesthetics were administered sequentially via peripheral venous access: midazolam 0.03 mg/kg, etomidate 0.3 mg/kg, sufentanil 0.3 μg/kg and rocuronium 1.2 mg/kg. After loss of consciousness and spontaneous breathing cessation, jaw-thrust maneuver and pressure-controlled ventilation (15 cmH₂O) were applied. Endotracheal intubation was performed with a video laryngoscope when the jaw was fully relaxed and the BIS value ranged from 40 to 60. Under direct visualization, the glottis was exposed gently to avoid dental injury. A well-lubricated endotracheal tube with appropriate size was inserted into the glottis. After removing the stylet and adjusting the insertion depth, the cuff was inflated properly. Correct tube position was confirmed by breath sounds and end-tidal carbon dioxide, followed by secure fixation. Mechanical ventilation parameters were set as tidal volume 6–10 mL/kg, oxygen flow 2 L/min, FiO2 60%, respiratory rate 12–20 breaths/min, and inspiratory-expiratory ratio 1: 2.
2.4.4. Intraoperative Anesthesia Maintenance
Combined intravenous-inhalational anesthesia was adopted. Target-controlled infusion (TCI) of propofol (plasma concentration: 2.0–4 μg/mL) and remifentanil (2–4 ng/mL) was administered, together with 0.5%–2.0% sevoflurane inhalation. Anesthetic dosage was titrated to maintain BIS at 40–60 and mean arterial pressure fluctuation within 20%. A quarter of the induction dose of rocuronium was supplemented hourly to sustain muscle relaxation. Before abdominal closure, additional sufentanil 0.1 μg/kg was given and sevoflurane was discontinued. All maintenance anesthetics were ceased 5 minutes before operation completion, with intravenous tropisetron 2 mg administered for postoperative nausea and vomiting prophylaxis.
2.4.5. Anesthesia Recovery
After skin suture, patients were transferred to the post-anesthesia care unit (PACU) for extubation once discharge criteria were met. When the VAS score ≥ 4 (recorded as Tv), patient-controlled intravenous analgesia (PCIA) was initiated with a loading dose of 2 mL. The pump contained 50 μg sufentanil in 100 mL solution, with a background infusion of 1 mL/h, a 2 mL bolus dose and a 15-minute lockout interval. Morphine 2 mg was intravenously administrated as rescue analgesia for persistent moderate-severe pain, and the first morphine administration time (Tm) was recorded. Patients with a Steward score ≥ 4 were transferred back to the ward, and PACU stay time (Tp) was documented.
2.5. Ward Management
Continuous electrocardiographic monitoring was performed for 48 hours postoperatively. Blinded medical staff conducted regular follow-ups to record vital signs at multiple time points: baseline (T0), PACU admission (T1), PACU discharge (T2), and 2, 4, 8, 12, 24, 48 hours after surgery (T3–T8). Postoperative VAS scores from T3 to T8 were assessed, while scores were omitted for sleeping patients. Tropisetron 2 mg was given for nausea and vomiting, with repeated doses if symptoms persisted. The CAM scale was assessed routinely at baseline and 2 h, 6 h, day 1 to day 3 after surgery, with additional evaluation and intervention conducted once POD-related symptoms occurred.
2.6. Observation Indicators
2.6.1. Primary Outcome
Cumulative morphine rescue consumption within 48 hours after surgery.
2.6.2. Secondary Outcomes
Time to first morphine rescue, time to the first VAS score ≥ 4, VAS scores from T3 to T8, incidence of postoperative delirium at 2 h, 6 h, day 1, day 2 and day 3 after surgery, and overall patient satisfaction.
2.6.3. Other Outcomes
Baseline characteristics including age, gender, height, weight and Body Mass Index (BMI); preoperative laboratory parameters such as hemoglobin, total bile acid, total bilirubin, albumin and estimated glomerular filtration rate. Perioperative vital signs including heart rate, blood pressure and SpO2 at designated time points. Intraoperative data contained operation duration, anesthetic dosage, fluid balance and vasoactive drug administration. Postoperative indicators involved extubation time, PACU stay length, incidences of shoulder pain and postoperative nausea and vomiting, tropisetron consumption, first ambulation time, anal exhaust time and hospital stay.
2.7. Data Analysis
2.7.1. Sample Size Calculation
Based on preliminary trial results, the 48-hour postoperative morphine consumption was 8.75±2.43 mg in Group S, 4.81±2.14 mg in Group ST, and 3.56±1.05 mg in Group STA. With a statistical power (1−β) of 0.8, a significance level (α) of 0.05 and a Cohen’s f effect size of 0.35, G*Power 3.1 was applied for one-way ANOVA calculation. A minimum of 55 participants per group (total 165 cases) was required. Allowing for a 10% dropout rate, a total of 186 patients were finally enrolled.
2.7.2. Statistical Methods
All data were analyzed using Excel 2016, SPSS 26.0 and GraphPad Prism 9.5.1. Normally distributed continuous variables were compared by one-way ANOVA with Bonferroni post-hoc correction. Non-normally distributed data were analyzed via the Kruskal-Wallis test. Repeated-measures ANOVA was adopted for time-series data such as VAS scores and vital signs, and interactive effects between time and grouping were analyzed when applicable. Pearson correlation analysis was used to assess the correlation between morphine rescue time and pain scores. A two-tailed P < 0.05 was defined as statistically significant.
3. Results
3.1. Comparison of Baseline Characteristics
There were no statistically significant differences in baseline characteristics among the three groups (P>0.05), including age, gender, BMI, ASA physical status classification, preoperative mini-mental state score, preoperative hemoglobin (Hb), total bilirubin (TBIL), total bile acid (TBA), albumin (ALB), and estimated glomerular filtration rate (eGFR) (
Table 1). Similarly, no significant intergroup differences were observed in operation duration, intraoperative blood loss, intraoperative fluid volume, anesthesia duration, or PACU stay time (P>0.05) (
Table 2).
Table 1. General Data Statistics of Patients in Each Group (<i></i>x±s).
n | Group S | Group ST | Group STA | F value | P value |
50 | 50 | 50 |
Sex (m/f) | 31/31 | 31/31 | 29/26 | 0.981 | 0.754 |
age | 71.35±4.17 | 71.16±3.86 | 70.45±4.42 | 0.331 | 0.718 |
BMI | 23.59±2.34 | 23.94±2.41 | 23.38±1.98 | 1.049 | 0.352 |
ASA | 2.52±0.50 | 2.63±0.49 | 2.65±0.50 | 0.883 | 0.601 |
IQ | 109.93±6.86 | 108.5±7.39 | 109.45±6.93 | 0.899 | 0.762 |
Hb (g/L) | 121.73±10.32 | 132.25±21.56 | 129.25±15.39 | 0.902 | 0.867 |
TBA (umol/L) | 5.51±1.04 | 5.93±2.01 | 5.13±2.92 | 1.219 | 0.910 |
TBIL (umol/L) | 12.33±4.10 | 13.21±3.95 | 13.63±4.12 | 0.945 | 0.758 |
ALB (g/L) | 45.54±7.70 | 42.32±9.39 | 47.36±6.26 | 1.819 | 0.110 |
eGFR (ml/min) | 105.56±10.66 | 103.23±11.29 | 112.15±8.74 | 0.841 | 0.473 |
Table 2. The results of operation, anesthesia, PACU time andIntra - operative fluid intake and output in three groups.
| Group S | Group ST | Group STA | F alue | P value |
Operation Duration (min) | 242.7±19.08 | 244.0±22.34 | 245.2±19.60 | 0.991 | 0.868 |
Anesthesia Duration (min) | 285.7±9.63 | 285.2±8.46 | 284.6±9.33 | 1.090 | 0.584 |
PACU Stay Time (min) | 68.28±11.72 | 72.32±9.786 | 66.82±10.99 | 0.805 | 0.542 |
Blood Loss (ml) | 305.8±113.8 | 305.6±102.5 | 295.8±117.8 | 0.769 | 0.656 |
Fluid Infusion (ml) | 2300±413.8 | 2480±400.4 | 2675±325.5 | 0.753 | 0.654 |
Urine Output (ml) | 455±161.2 | 439±138.8 | 748±174.4 | 26.27 | <0.001 |
3.2. Intraoperative Anesthetic Consumption Among the Three Groups
Compared with Group S and Group ST, the STA group presented significantly lower intraoperative dosages of remifentanil, sufentanil and propofol (P < 0.0001), while no significant difference was found in sevoflurane consumption (P = 0.3410). Further analysis showed that remifentanil usage was markedly reduced in Group ST relative to Group S (P < 0.0001), whereas no statistical differences were observed in sufentanil and propofol doses between Group ST and Group S (P > 0.05). Detailed data are shown in
Table 3.
Table 3. Intraoperative consumption of sufentanil, remifentanil, propofol and sevoflurane in three groups (x±s).
| Group S | Group ST | Group STA | F value | P value |
Sufentanil (μg) | 45.81±6.32 | 41.58±4.23 | 34.07±3.16*# | 89.521 | <0.001 |
Remifentanil (μg) | 1244.34±135.34 | 996.64±180.25a | 689.63±112.35*# | 20.822 | <0.001 |
Propofol (mg) | 1411.38±206.04 | 1389.56±134.22 | 1044.77±75.98*# | 90.181 | <0.001 |
Sevoflurane (mL) | 65.22±5.23 | 61.32±4.27 | 60.72±7.41 | 1.080 | 0.341 |
3.3. Comparison of Primary and Secondary Outcomes Among the Three Groups
3.3.1. Morphine Rescue Consumption, First Rescue Time and Time to First VAS ≥ 4
Compared with Group S, both Group ST and Group STA exhibited significantly lower 48-hour postoperative morphine rescue requirements (P < 0.05). The STA group showed slightly less morphine consumption than the ST group, without statistical significance. Although the initial pain intensity was comparable, notable differences were observed in the time to first VAS score ≥ 4. This interval was markedly prolonged in the STA group when compared with the ST and S groups (P < 0.05), and was also significantly longer in the ST group than in the S group (P < 0.05). In addition, the time to first morphine rescue was positively correlated with the time to first VAS ≥ 4 across all three groups. Relevant data are presented in
Table 4.
Table 4. Results of morphine salvage dose within 48 hours and first VAS ≥4 in three groups ().
| Group S | Group ST | Group STA | F value | P value |
48-hour rescue (mg) | 8.75±2.43 | 4.806±2.14a | 3.56±1.05* | 70.092 | <0.001 |
First VAS ≥ 4 | 125.71±9.63 | 205.2±8.46a | 284.26±9.33*# | 275.031 | <0.001 |
First rescue | 385.52±59.73 | 441.01±47.17 | 537.24±38.84*# | 163.220 | <0.001 |
score at first VAS ≥ 4 | 4.65±0.58 | 4.42±0.34 | 4.25±0.23 | 1.571 | 0.653 |
3.3.2. Postoperative VAS Scores, CAM Scores and Patient Satisfaction
From T3 to T8, the STA group presented marginally lower VAS scores than the ST group and significantly lower scores than the S group, with statistically significant intergroup differences (
P < 0.05) (
Table 5). At 2 and 6 hours postoperatively, CAM scores in the STA group were significantly higher than those in the ST and S groups (
P < 0.05). The ST group had slightly higher CAM scores than the S group, but the difference was not statistically significant (
P > 0.05).
During postoperative days 1 to 3, the mean CAM scores remained above 22 in all three groups. Occasional CAM scores below 19 were noted in the ST and S groups, whereas no such cases occurred in the STA group, with no significant overall intergroup difference. Patient satisfaction was markedly higher in the STA group than in the ST and S groups
(P < 0.05), while no significant difference was found between the ST and S groups. Detailed data are shown in
Table 6.
Table 5. Results of VAS scores for T3~T8 in three groups of patients ().
| Group S | Group ST | Group STA | F value | P value |
T3 VAS | 5.03±1.40 | 4.43±0.45 | 3.14±0.84*# | 45.719 | <0.001 |
T4 VAS | 5.53±1.94 | 4.25±1.27 | 3.06±0.86*# | 61.933 | <0.001 |
T5 VAS | 5.22±1.76 | 4.33±1.04 | 3.03±0.77*# | 55.646 | <0.001 |
T6 VAS | 4.56±1.39 | 3.79±0.97 | 3.12±0.80*# | 46.125 | <0.001 |
T7 VAS | 4.03±1.52 | 3.93±0.95 | 3.15±0.77*# | 48.331 | <0.001 |
T8 VAS | 3.52±1.07 | 2.44±1.11 | 2.17±0.82*# | 42.726 | <0.001 |
Table 6. Postoperative delirium scores and satisfaction scores at discharge for the three groups of patients ().
after surgery | Group S | Group ST | Group STA | F value | P value |
2h CAM | 17.53±1.12 | 19.27±2.18 | 21.82±2.08*# | 74.827 | <0.001 |
6h CAM | 18.35±1.11 | 21.36±1.87 | 26.14±4.10*# | 45.534 | <0.001 |
1d CAM | 28.19±4.17 | 28.93±3.84 | 29.13±3.83 | 1.526 | 0.216 |
2d CAM | 28.25±1.39 | 29.91±0.97 | 28.94±4.80 | 1.738 | 0.487 |
3d CAM | 30.14±4.58 | 30.95±6.03 | 31.12±5.27 | 2.093 | 0.119 |
Satisfaction score | 6.33±1.00 | 6.54±1.11 | 8.44±0.88*# | 78.216 | <0.001 |
3.4. Adverse Reactions and Postoperative Recovery Outcomes
No significant differences were observed among the three groups in the incidence of postoperative nausea and vomiting, tropisetron consumption, time to first anal exhaust, or perioperative changes in total bile acid (
P > 0.05), as summarized in
Table 7. Compared with the ST and S groups, the STA group achieved earlier first ambulation, milder shoulder pain, and shorter hospital stay, with statistically significant differences (
P < 0.05). No obvious differences were found between the ST group and the S group (
P > 0.05) (
Table 8).
Table 7. The results of postoperative nausea and vomiting, the use of ondansetron and the time of flatus in three groups of patients ().
| Group S | Group ST | Group STA | F value | P value |
Nausea and vomiting (cases) | 55 (11) | 62 (12) | 62 (12) | 12.323 | 0.735 |
Tropisetron dosage (mg) | 2.75±1.57 | 2.48±1.24 | 2.72±1.51 | 0.761 | 0.469 |
Time to first flatus (h) | 27.41±2.90 | 26.95±3.28 | 26.89±3.14 | 0.515 | 0.588 |
Table 8. The results of the three groups of patients with the time of getting out of bed, the incidence of shoulder pain and the length of hospital.
| Group S | Group ST | Group STA | F value | P value |
First ambulation (h) | 37.70±3.51 | 37.02±3.65 | 32.20±2.50*# | 47.478 | <0.001 |
shoulder pain (cases) | Mild (23) Moderate (10) Severe (1) | Mild (21) Moderate (8) | Mild (10) Moderate (1) | 31.425 | <0.001 |
TBA variability | 2.34±0.33 | 2.14±0.69 | 2.59±0.652 | 0.067 | 0.934 |
Hospitalization (days) | 9.13±1.30 | 9.02±1.52 | 7.02±1.63*# | 4.159 | 0.016 |
4. Discussion
With population aging accelerating, balancing postoperative pain control and enhanced recovery has become a critical clinical concern for elderly patients
| [12] | Vahanian, alec; beyersdorf, friedhelm; praz, fabien; et, al. 2021 esc/eacts guidelines for the management of valvular heart disease: developed by the task force for the management of valvular heart disease of the european society of cardiology (esc) and the european association for cardio-thoracic surgery (eacts). [miscellaneous article, j]. european heart journal. 2022, vol. 43(no. 7): 561-632. https://doi.org/10.1016/j.rec.2022.05.006 |
[12]
. Due to progressive organ dysfunction, reduced drug metabolism, and multiple comorbidities, analgesic strategies in older adults must balance efficacy and safety. This prospective randomized controlled trial evaluated the multimodal analgesic efficacy of transversus abdominis plane block (TAPB) combined with intravenous paracetamol mannitol in elderly patients undergoing laparoscopic radical gastrectomy. Compared with opioid monotherapy (Group S) and TAPB combined with opioids (Group ST), the multimodal regimen in Group STA markedly reduced postoperative opioid consumption, prolonged analgesic duration, and improved early postoperative CAM scores for delirium assessment. These findings confirm the synergistic advantages of multimodal analgesia and provide evidence-based guidance for optimizing perioperative pain management and implementing enhanced recovery after surgery (ERAS) protocols in elderly surgical populations.
As an effective regional anesthetic technique, ultrasound-guided TAPB blocks anterior abdominal wall neural innervation by depositing local anesthetics within the fascial plane between the internal oblique and transversus abdominis muscles, alleviating somatic incision pain and preserving perioperative immune function
| [13] | Jingwei dai, shiwen lin, xiaoguang cui, et, al. the effects of ultrasound-guided qlb and tapb combined with opioid-free anesthesia (ofa) on clinical efficacy of the patients undergoing abdominal surgery. heliyon. 2023 oct 11; 9(10): e20878. |
[13]
. Nevertheless, pain following laparoscopic gastrectomy is multifactorial, with visceral discomfort and inflammatory pain accounting for most postoperative distress induced by surgical traction and carbon dioxide pneumoperitoneum-related peritoneal inflammation
| [14] | Yoshitomo yanagimoto, shuji takiguchi, yasuhiro miyazaki, et al. comparison ofpain management after laparoscopic distal gastrectomy with andwithout epidural analgesia [j]. surg today, 2015, 46(2): 1-6. https://doi.org/10.1007/s00595-015-1162-y |
[14]
. Conventional TAPB alone cannot sufficiently control visceral and persistent inflammatory pain, which explains the sustained opioid requirement observed in Group ST.
The combined administration of paracetamol mannitol exerts complementary analgesic and anti-inflammatory effects. Paracetamol centrally inhibits cyclooxygenase-2 activity and modulates endogenous cannabinoid pathways to mitigate spinal neuronal sensitization and persistent nociceptive signaling
| [10] | Christophe mallet, jules desmeules, rassa pegahi, et al. an updated review on the metabolite (am404)-mediated central mechanism of action of paracetamol (acetaminophen): experimental evidence and potential clinical impact [j]. j pain res, 2023, 29, 16: 1081-1094.
https://doi.org/10.2147/JPR.S393809 |
[10]
. It also attenuates local surgical inflammation by suppressing prostaglandin E2 production and NF-κB pathway activation, thereby augmenting the local anti-inflammatory effects of TAPB. Furthermore, paracetamol metabolites selectively modulate visceral pain transmission, which is particularly beneficial for laparoscopic abdominal surgery. In the present study, the STA group demonstrated substantially lower 48-hour morphine rescue dosage and a prolonged interval to the first VAS score ≥ 4, accompanied by consistently reduced resting VAS scores across early postoperative time points. These outcomes are consistent with previous research investigating multimodal analgesia for laparoscopic gastrointestinal surgery, while intravenous paracetamol offers superior bioavailability and rapid onset compared with oral formulations
| [7] | He zj, xie kj, huang zx, et al. effect of low-opioid regimens on the incidence of postoperative delirium in elderly patients with gastric cancer surgery [j]. national medical journal of china, 2022, 102(05): 326-331. |
[7]
. Reduced intraoperative sufentanil consumption in the STA group also supports the preemptive analgesic effect of preoperative paracetamol, which blunts central nociceptive sensitization and decreases perioperative opioid demand
| [16] | Young-eun moon, yoon-ki lee, jaemin lee,, et al. the effects of preoperative intravenous acetaminophen in patients undergoing abdominal hysterectomy [j]. arch gynecol obstet, 2011, 284(6): 1455-1460. |
[16]
.
Postoperative delirium (POD) is a prevalent and prognostically unfavorable neurological complication among elderly surgical patients, closely linked to severe pain, excessive inflammatory responses, and high opioid exposure
| [17] | Takefumi itami, kazuyoshi yamamoto, ukinori kurokawa, et al. aso visual abstract: assessing the risk of postoperative delirium through comprehensive geriatric assessment and eastern cooperative oncology group performance status in elderly patients with gastric cancer [j]. ann surg oncol (2024) 31: 9067–9068.
https://doi.org/10.1245/s10434-024-16034-w Epub 2024 Oct 7. |
[17]
. Higher early postoperative CAM scores in the STA group indicated a lower early POD risk, primarily attributable to comprehensive pain relief and decreased intraoperative opioid administration. Uncontrolled surgical pain triggers neuroinflammation by elevating proinflammatory cytokines, disrupting blood-brain barrier integrity, and impairing neuronal function, all of which contribute to delirium development
| [9] | Miao zhu, wenchao sun. analgesic effects of ropivacaine combined with dexmedetomidine in transversus abdominis plane block in patients undergoing laparoscopic cholecystectomy: a systematic review and meta-analysis [j]. j perianesth nurs, 2023 jun, 38(3), 493–503.
https://doi.org/10.1016/j.jopan.2022.09.003 |
| [14] | Yoshitomo yanagimoto, shuji takiguchi, yasuhiro miyazaki, et al. comparison ofpain management after laparoscopic distal gastrectomy with andwithout epidural analgesia [j]. surg today, 2015, 46(2): 1-6. https://doi.org/10.1007/s00595-015-1162-y |
[9, 14]
. Excessive opioid use further exacerbates neurocognitive disturbance through glial activation, immune suppression, and cholinergic dysfunction
| [15] | Mikami jota，takiguchi shuji，miyazaki yasuhiro，et al. novel management of postoperative pain using only oral analgesics after ladg [j]. surgery today. 2016, vol. 46(no. 1): 117-122.
https://doi.org/10.1007/s00595-015-1155-x Epub 2015 Mar 24. |
[15]
. Although TAPB partially reduces opioid consumption, continuous infusion of short-acting remifentanil in the ST group may still heighten neurological excitability, consistent with earlier clinical observations
| [18] | Ba yz, qi f. mechanism and prevention progress of remifentanil-induced hyperalgesia [j]. medical frontier, 2025, 15(03): 27-30. |
[18]
. In addition, the combined use of paracetamol and long-acting ropivacaine yields a favorable metabolic profile suited to age-related physiological changes. The mannitol component in the formulated paracetamol solution also alleviates cerebral edema caused by carbon dioxide retention during laparoscopy, as reflected by increased urine output in the STA group. After the early postoperative period, CAM scores became comparable across groups, indicating a critical early therapeutic window for POD prevention.
Concerns regarding paracetamol-associated hepatotoxicity remain widespread; however, this study verified the safety of therapeutic-dose intravenous paracetamol in elderly participants. No significant perioperative changes in total bile acid levels were detected in the STA group, supporting stable hepatic function
. Intravenous administration avoids first-pass hepatic metabolism, limiting the production of toxic metabolites and lowering liver injury risk at standard clinical doses
| [20] | Wojciech weig, andrzej bieryło, monika wielgus, et al. intravenous acetaminopheneffect on postoperative narcotic analgesic demand after elective cesarean section [j]. novel biomed, 2016，4(1): 13-17.
https://doi.org/10.1097/01.md.0000496599.67747.13 |
[20]
. Moreover, paracetamol did not delay gastrointestinal recovery or increase adverse abdominal events, conferring advantages over nonsteroidal anti-inflammatory drugs that carry elevated anastomotic leakage risks
| [10] | Christophe mallet, jules desmeules, rassa pegahi, et al. an updated review on the metabolite (am404)-mediated central mechanism of action of paracetamol (acetaminophen): experimental evidence and potential clinical impact [j]. j pain res, 2023, 29, 16: 1081-1094.
https://doi.org/10.2147/JPR.S393809 |
| [11] | Li jj, zhao m, fu yq, et al. research progress on preoperative frailty and risk of postoperative delirium in elderly patients [j]. practical geriatrics, 2023, 37(09): 951-955. |
[10, 11]
. Hemodynamic stability was maintained throughout surgery in all groups, confirming the cardiovascular safety of this multimodal strategy. The fixed 1 g preoperative dose adopted in this trial complies with current domestic expert consensus on low-opioid multimodal analgesia for elderly patients, though individualized dosage adjustment is recommended for those with advanced liver disease or malnutrition
.
Several limitations of this study should be acknowledged. The single-center design may limit generalizability, and subtle variations in surgical techniques and perioperative management were not fully controlled. Routine liver function monitoring was restricted to conventional biochemical indicators, without advanced metabolic or mitochondrial injury biomarkers for detailed hepatotoxicity evaluation
| [22] | Ning liu, jiao feng, yang lv, et al. role of bile acids in the diagnosis and progression of livercirrhosis: a prospective observational study [j]. exp ther med, 2019, 18(5): 4058-4066.
https://doi.org/10.3892/etm.2019.8011 Epub 2019 Sep 17. |
[22]
. Additionally, only a single fixed preoperative dose of paracetamol was applied, and optimal infusion regimens and drug concentration ratios require further exploration
| [23] | Patricia m lavand'homme, henrik kehlet, narinder rawal. et al. pain management after total knee arthroplasty: procedure specific postoperative pain management recommendations [j]. eur j anaesthesiol. 2022 sep 1; 39(9): 743-757.
https://doi.org/10.1097/EJA.0000000000001691 Epub 2022 Jul 20. |
[23]
. This study focused exclusively on short-term postoperative outcomes; long-term cognitive changes, chronic pain incidence, and oncological prognosis remain to be clarified through extended follow-up.
5. Conclusion
This multimodal analgesic protocol combining TAPB and preoperative paracetamol effectively optimizes perioperative pain management, reduces opioid reliance, accelerates early postoperative rehabilitation, and improves patient satisfaction. It also lowers the early risk of postoperative delirium via anti-inflammatory, central analgesic, and opioid-sparing mechanisms, with a favorable safety profile in elderly patients with declined hepatic and renal function. This low-opioid, ERAS-compatible regimen is feasible for widespread clinical application, especially in primary hospitals. Further high-quality multicenter trials and personalized protocol optimization will help refine standardized perioperative analgesic strategies for elderly abdominal surgery patients.
Abbreviations
BMI | Body Mass Index |
TAPB | Transversus Abdominis Plane Block |
ERAS | Enhanced Recovery After Surgery |
CAM | Confusion Assessment Method |
POD | Postoperative Delirium |
VAS | Visual Analogue Scale |
ORAE | Opioid-Related Adverse Events |
Author Contributions
Zhifu Zhao: Conceptualization, Data curation, Formal Analysis, Funding acquisition, Methodology, Visualization, Writing – original draft, Writing – review & editing
Li Liu: Data curation, Investigation, Methodology, Project administration, Resources, Validation, Visualization, Writing – original draft, Writing – review & editing
Xianjie Zhang: Conceptualization, Funding acquisition, Investigation, Project administration, Resources, Supervision, Validation
Feng Ju: Data curation, Investigation, Resources, Software, Supervision, Validation
Wenhu Zhai: Data curation, Formal Analysis, Funding acquisition, Investigation
Dan Zhou: Project administration, Resources, Software, Supervision, Validation, Visualization
Funding
This study received funding from the China Red Cross Foundation Medical Empowerment Public Welfare Special Fund Analgesia Action Clinical Research Project (Grant No. CRCF-YXFN-202301018). The funder had no role in the study design, data collection, analysis, interpretation, manuscript writing, or decision to submit the article for publication.
Conflicts of Interest
The authors declare no conflicts of interest.
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Cite This Article
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APA Style
Zhao, Z., Liu, L., Zhang, X., Ju, F., Zhai, W., et al. (2026). Clinical Study on the Efficacy and Safety of Paracetamol Combined with TAPB Nerve Block in Elderly Patients Undergoing Gastrointest. Journal of Surgery, 14(3), 39-48. https://doi.org/10.11648/j.js.20261403.11
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Zhao, Z.; Liu, L.; Zhang, X.; Ju, F.; Zhai, W., et al. Clinical Study on the Efficacy and Safety of Paracetamol Combined with TAPB Nerve Block in Elderly Patients Undergoing Gastrointest. J. Surg. 2026, 14(3), 39-48. doi: 10.11648/j.js.20261403.11
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AMA Style
Zhao Z, Liu L, Zhang X, Ju F, Zhai W, et al. Clinical Study on the Efficacy and Safety of Paracetamol Combined with TAPB Nerve Block in Elderly Patients Undergoing Gastrointest. J Surg. 2026;14(3):39-48. doi: 10.11648/j.js.20261403.11
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@article{10.11648/j.js.20261403.11,
author = {Zhifu Zhao and Li Liu and Xianjie Zhang and Feng Ju and Wenhu Zhai and Dan Zhou},
title = {Clinical Study on the Efficacy and Safety of Paracetamol Combined with TAPB Nerve Block in Elderly Patients Undergoing Gastrointest},
journal = {Journal of Surgery},
volume = {14},
number = {3},
pages = {39-48},
doi = {10.11648/j.js.20261403.11},
url = {https://doi.org/10.11648/j.js.20261403.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.js.20261403.11},
abstract = {Objective This study explored the efficacy of paracetamol mannitol injection combined with TAPB for postoperative pain relief in elderly patients after laparoscopic radical gastrectomy, as this combined regimen also reduces postoperative complications including delirium, nausea, vomiting and impaired wound healing, offering a novel strategy for postoperative pain management in such patients. Methods This prospective study included 150 elderly patients (≥65 years) undergoing laparoscopic radical gastrectomy, who were randomly assigned to three groups: sufentanil alone (S), sufentanil plus TAPB (ST), and sufentanil combined with TAPB and paracetamol mannitol (STA). All patients received routine vital sign and BIS monitoring with standardized vascular access establishment before anesthesia. Each group received corresponding preoperative interventions, and multiple perioperative indicators were compared, including opioid consumption, hemodynamic parameters, surgical and anesthetic variables, postoperative pain scores, adverse events, recovery outcomes and patient satisfaction. Results No significant intergroup differences were found in baseline demographics, perioperative indicators, intraoperative vital signs, vasoactive agent use, postoperative adverse reactions, gastrointestinal recovery indicators and bile acid levels among the three groups (all P>0.05). Compared with Group S and ST, the STA group presented decreased intraoperative consumption of sufentanil, remifentanil and propofol, reduced postoperative morphine requirement, prolonged time to the first moderate-severe pain, lower postoperative visual analogue scale (VAS) pain scores, higher early postoperative Confusion Assessment Method (CAM) scores without postoperative delirium, superior patient satisfaction, milder shoulder pain, earlier out-of-bed activity and shorter hospital stay; additionally, the ST group consumed fewer intraoperative anesthetics and exhibited better analgesic effects than the S group, while the slight difference in morphine consumption between the STA and ST groups was not statistically significant. Conclusions Combined application of TAPB and paracetamol mannitol can effectively alleviate early postoperative pain, cut down opioid consumption, relieve pain-induced restrictions on out-of-bed activity and improve satisfaction in elderly patients undergoing laparoscopic radical gastrectomy, which greatly optimizes postoperative pain management; meanwhile, paracetamol mannitol brings no extra risks to gastrointestinal function recovery or gastrointestinal bleeding, ensuring its safe application for postoperative analgesia in this elderly patient population.},
year = {2026}
}
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TY - JOUR
T1 - Clinical Study on the Efficacy and Safety of Paracetamol Combined with TAPB Nerve Block in Elderly Patients Undergoing Gastrointest
AU - Zhifu Zhao
AU - Li Liu
AU - Xianjie Zhang
AU - Feng Ju
AU - Wenhu Zhai
AU - Dan Zhou
Y1 - 2026/05/18
PY - 2026
N1 - https://doi.org/10.11648/j.js.20261403.11
DO - 10.11648/j.js.20261403.11
T2 - Journal of Surgery
JF - Journal of Surgery
JO - Journal of Surgery
SP - 39
EP - 48
PB - Science Publishing Group
SN - 2330-0930
UR - https://doi.org/10.11648/j.js.20261403.11
AB - Objective This study explored the efficacy of paracetamol mannitol injection combined with TAPB for postoperative pain relief in elderly patients after laparoscopic radical gastrectomy, as this combined regimen also reduces postoperative complications including delirium, nausea, vomiting and impaired wound healing, offering a novel strategy for postoperative pain management in such patients. Methods This prospective study included 150 elderly patients (≥65 years) undergoing laparoscopic radical gastrectomy, who were randomly assigned to three groups: sufentanil alone (S), sufentanil plus TAPB (ST), and sufentanil combined with TAPB and paracetamol mannitol (STA). All patients received routine vital sign and BIS monitoring with standardized vascular access establishment before anesthesia. Each group received corresponding preoperative interventions, and multiple perioperative indicators were compared, including opioid consumption, hemodynamic parameters, surgical and anesthetic variables, postoperative pain scores, adverse events, recovery outcomes and patient satisfaction. Results No significant intergroup differences were found in baseline demographics, perioperative indicators, intraoperative vital signs, vasoactive agent use, postoperative adverse reactions, gastrointestinal recovery indicators and bile acid levels among the three groups (all P>0.05). Compared with Group S and ST, the STA group presented decreased intraoperative consumption of sufentanil, remifentanil and propofol, reduced postoperative morphine requirement, prolonged time to the first moderate-severe pain, lower postoperative visual analogue scale (VAS) pain scores, higher early postoperative Confusion Assessment Method (CAM) scores without postoperative delirium, superior patient satisfaction, milder shoulder pain, earlier out-of-bed activity and shorter hospital stay; additionally, the ST group consumed fewer intraoperative anesthetics and exhibited better analgesic effects than the S group, while the slight difference in morphine consumption between the STA and ST groups was not statistically significant. Conclusions Combined application of TAPB and paracetamol mannitol can effectively alleviate early postoperative pain, cut down opioid consumption, relieve pain-induced restrictions on out-of-bed activity and improve satisfaction in elderly patients undergoing laparoscopic radical gastrectomy, which greatly optimizes postoperative pain management; meanwhile, paracetamol mannitol brings no extra risks to gastrointestinal function recovery or gastrointestinal bleeding, ensuring its safe application for postoperative analgesia in this elderly patient population.
VL - 14
IS - 3
ER -
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