Analgesic efficacy of thoracic paravertebral block in elderly gastric cancer patients and its impact on homeostasis

Abstract

BACKGROUND

Older patients undergoing laparoscopic radical gastrectomy (LRG) for gastric cancer (GC) often experience intense postoperative pain and stress responses, compromising recovery and homeostasis.

AIM

To analyze the analgesic efficacy of thoracic paravertebral block (TPVB) in older patients undergoing LRG for GC and its impact on homeostasis.

METHODS

In this study, we used the medical records of 227 older patients with GC who underwent LRG at our hospital from January 2018 to January 2025. Patients received either TPVB plus general anesthesia (combination group, n = 120) or general anesthesia alone (control group, n = 107). Outcomes included operative time, extubation time, visual analog scale (VAS) scores, incidence of adverse reactions, white blood cell count, neutrophil percentage, interleukin-6 levels, arterial partial pressure of O₂, partial pressure of CO₂, blood lactate, and liver and kidney function indices. Multiple linear regression analysis was used to explore the factors influencing postoperative pain.

RESULTS

No significant inter-group differences were found in the operative or extubation times (P > 0.05). At 6, 24, and 48 hours postoperatively, the combination group had significantly lower VAS scores than the control group (all P < 0.05). At 72 hours postoperatively, the combination group showed significantly lower white blood cell count, neutrophil percentage, and interleukin-6 levels than the control group (all P < 0.05). At 12 hours postoperatively, the combination group showed significantly lower levels of partial pressure of CO₂ and lactate than the control group (both P < 0.001), whereas no significant inter-group difference was found in partial pressure of O₂ (P > 0.05). No significant differences were observed in the alanine aminotransferase, aspartate aminotransferase, serum creatinine, or blood urea nitrogen levels between both groups preoperatively or at 24 and 72 hours postoperatively. The combination group presented a significantly lower incidence of postoperative nausea and vomiting, and overall complication rate than the control group (P < 0.05). Multiple linear regression identified the anesthesia method (β = -1.567, 95% confidence interval: -1.639 to -1.495, P < 0.001) as the only independent influencing factor for postoperative pain scores.

CONCLUSION

TPVB plus general anesthesia provided superior postoperative analgesia, effectively mitigated postoperative inflammatory responses, improved pulmonary ventilation and tissue perfusion, maintained homeostasis, and reduced postoperative nausea and vomiting incidences.

Key Words: Thoracic paravertebral block; Radical gastrectomy for gastric cancer; Postoperative analgesia; Inflammatory factors; Liver and kidney function

Core Tip: In elderly patients undergoing laparoscopic radical gastrectomy for gastric cancer, the combination of thoracic paravertebral block and general anesthesia provides superior postoperative analgesia, as evidenced by significantly lower visual analog scale scores at 6, 24, and 48 hours. This approach also effectively mitigates the inflammatory response (lower white blood cell, neutrophil percentage, and interleukin-6), improves physiological homeostasis (lower partial pressure of CO₂ and blood lactate), and reduces the incidence of postoperative nausea and vomiting and overall complications. Multiple linear regression identifies the anesthesia method as the sole independent factor for postoperative pain, while the combination shows no significant additional impact on liver and kidney function.

INTRODUCTION

As the population ages, the incidence of gastric cancer (GC) in older patients has increased substantially, posing new challenges for clinical management[1]. Although radical gastrectomy is the preferred treatment for GC[2], older patients are often frail, immunocompromised, and burdened with comorbidities, increasing surgical complexity and anesthetic risk[3]. Traditional open thoracic surgery is associated with significant trauma, severe postoperative pain, and a high risk of hemodynamic fluctuations[4]. Laparoscopic surgery, as a minimally invasive technique, leads to varying degrees of local tissue damage, triggering postoperative stress responses and suppressing immune function[5].

Postoperative analgesia is crucial for perioperative management. Traditional multimodal analgesia often relies on opioids; however, older patients exhibit increased sensitivity to opioids and are more susceptible to related adverse effects, such as respiratory depression, nausea, and vomiting[6,7]. Peripheral nerve block involves the local injection of anesthetic agents to block pain signal transmission along peripheral nerves, thereby alleviating pain[8]. Thoracic paravertebral nerves belong to the peripheral nerve roots. Thoracic paravertebral block (TPVB) involves injecting local anesthetics into the paravertebral space via a puncture needle, allowing the drug to act on the spinal nerve roots to achieve analgesic effects, thereby maintaining hemodynamic stability and promoting patient recovery[9]. Previous research has suggested that TPVB suppresses excessive surgical stress responses and modulates immune and inflammatory responses[10]. Therefore, this study systematically evaluated the perioperative value of TPVB plus general anesthesia in older patients undergoing laparoscopic radical gastrectomy (LRG) for GC to optimize perioperative management strategies for older patients with GC.

MATERIALS AND METHODS

Data source

Following approval from the Medical Ethics Committee of our hospital, this study analyzed the clinical data of 250 older patients with GC who underwent LRG at our hospital from January 2018 to January 2025. The sample size was determined based on the principle of feasibility by including all patients who met the inclusion criteria within the defined study period at our hospital.

Inclusion and exclusion criteria

Inclusion criteria: (1) Age ≥ 60 years; (2) Pathologically diagnosed with primary GC and underwent LRG for GC; (3) American Society of Anesthesiologists (ASA) classification of I-II; (4) body mass index (BMI) = 18-27 kg/m²; (5) No cognitive impairment; and (6) Complete clinical data.

Exclusion criteria: (1) Infection or deformity at the TPVB puncture site; (2) Allergy to any medications adopted in the study; (3) Long-term use of analgesics or history of chronic pain; (4) Severe hepatic or renal dysfunction; (5) Distant metastasis of the tumor or palliative surgery; and (6) During pregnancy or lactation.

Grouping

We selected 227 older patients with GC. Based on the intraoperative anesthesia method, 120 patients who received TPVB plus general anesthesia were assigned to the combination group, whereas 107 patients who received general anesthesia alone were assigned to the control group.

Regarding the determination of anesthesia methods, the choice between TPVB plus general anesthesia and general anesthesia alone was primarily based on the anesthesiologist’s preference and patient consultation. The TPVB was routinely recommended for all eligible older patients who underwent LRG for GC during the study period. Patients who agreed to undergo TPVB and had no contraindications were assigned to the combination group, whereas those who declined TPVB or had contraindications received general anesthesia alone.

Procedure protocol

All patients underwent LRG for GC. In the operating room, patients were monitored for vital signs and administered intravenous injections of etomidate 0.2 mg/kg, midazolam 0.02-0.05 mg/kg, cisatracurium 0.2 mg/kg, and sufentanil 0.4 μg/kg. All patients underwent endotracheal intubation, and were placed on mechanical ventilation; respiratory rate of 10-12 breaths/minute, tidal volume of 8-10 mL/kg, inspiratory-to-expiratory ratio of 1:2, and maintenance of end-tidal carbon dioxide at 30-40 mmHg. Patients in the combination group were placed in the right lateral decubitus position. Using a portable ultrasound system (LOGIQ e NextGen, United States) with a high-frequency probe aligned parallel to the intercostal space, needles were inserted bilaterally at the T7, T8, and T9 segments. In each segment, 5 mL of 0.5% ropivacaine was injected. Both groups were maintained under total intravenous anesthesia with continuous infusions of remifentanil 0.1-0.3 μg/(kg × hour) and propofol 3-6 mg/(kg × hour). Postoperatively, intravenous analgesia was administered using flurbiprofen axetil (100 mg) plus sufentanil (3 μg/kg).

Outcome measures

Primary outcome measures: (1) Analgesic effect: The visual analog scale (VAS) was used to assess pain at rest and 6, 24, and 48 hours postoperatively. The VAS scores range from 0 (no pain) to 10 (severe pain), with higher scores indicating more intense pain[11]; (2) Systemic stress and inflammatory response: White blood cell (WBC) count, neutrophil percentage (NEUT%), and interleukin-6 (IL-6) levels were analyzed and compared between both groups. Peripheral venous blood samples (5 mL) were collected from the patients after overnight fasting preoperatively and 12, 24, and 48 hours postoperatively. WBC count and NEUT% were measured using a Sysmex XN-550 automated hematology analyzer (Sysmex Corporation, Kobe, Japan). IL-6 was determined via enzyme-linked immunosorbent assay using the Quantikine^® enzyme-linked immunosorbent assay human IL-6 Immunoassay kit (catalog number: D6050) from R&D Systems, United States. All procedures were performed in strict accordance with manufacturer’s instructions; (3) Blood lactate (Lac) and arterial blood gas analyses: Lacand arterial blood gas parameters [arterial partial pressure of O₂ (PaO₂) and partial pressure of CO₂ (PaCO₂)] were analyzed. Preoperatively and 12 hours postoperatively, 5 mL of whole blood was collected via radial artery puncture using a dedicated arterial blood collection tube containing a lithium heparin anticoagulant. Samples were analyzed within 15 minutes of collection using a Roche Diagnostics Cobas b123 fully automated blood gas analyzer (Roche Diagnostics GmbH, Mannheim, Germany); and (4) Liver and kidney function: Fasting venous blood samples (5 mL) were collected from patients preoperatively and 24 and 72 hours postoperatively. Alanine aminotransferase and aspartate aminotransferase levels were measured using the enzymatic rate method, and serum creatinine and blood urea nitrogen levels were determined using colorimetric assays. All measurements were performed using a Hitachi LABOSPECT 008AS fully automated biochemical analyzer (Hitachi High-Tech Corporation, Tokyo, Japan) with matching reagents.

Secondary outcome measures: (1) Baseline characteristics: Baseline clinical characteristics, including age, sex, BMI, ASA classification, clinical stage, and surgical approach, were analyzed and compared between both groups; (2) Recovery quality indices: The operative time and time from the end of surgery to successful extubation were analyzed and compared between both groups; (3) Safety: Anesthesia- or analgesia-related adverse reactions occurring within 48 hours postoperatively were analyzed, including nausea and vomiting, pruritus, respiratory depression, and urinary retention; and (4) Factors influencing postoperative pain intensity: Multiple linear regression analysis was performed using the VAS score at 24 hours postoperatively as the dependent variable.

Statistical analysis

Statistical analysis was performed using SPSS and graph plotting was performed using GraphPad Prism 7. Measurement data conforming to a normal distribution are presented as mean ± SD, with inter-group comparisons conducted using t-test. Categorical data are presented as n (%), with inter-group comparisons performed using the χ² or Fisher’s exact test. Repeated-measurement data were analyzed using repeated-measures analysis of variance for overall comparisons. Multiple linear regression analysis was conducted to identify the independent factors influencing postoperative pain. Statistical significance was set at P < 0.05.

RESULTS

Clinical baseline data

Analysis of clinical baseline data between both groups revealed no notable differences in age, sex, BMI, ASA classification, clinical stage, and surgical approach (all P > 0.05, Table 1).

Table 1 Patient clinical characteristics.

Factors	Age (year)	Sex		BMI	ASA classification		Clinical stage		Surgical approach
		Male	Female		Class I	Class II	Stage I	Stage II	Total gastrectomy	Distal gastrectomy
Control group (n = 107)	66.64 ± 1.40	57	50	23.10 ± 1.71	66	41	71	36	55	52
Combination group (n = 120)	66.70 ± 1.22	51	69	22.78 ± 1.58	78	42	89	31	64	52
χ2/t	0.426	2.631		1.442	0.268		1.659		0.318
P value	0.670	0.105		0.1506	0.604		0.198		0.573

BMI: Body mass index.

Surgical parameters

No notable differences were observed between the two groups regarding operative (166.6 ± 18.3 minutes vs 166.8 ± 17.6 minutes, P = 0.950) and extubation times (19.9 ± 1.4 minutes vs 19.8 ± 1.4 minutes, P = 0.546) (Figure 1).

Figure 1 Comparison of operative and extubation times between the two groups. A: Operative time; B: Extubation time. NS: Not significant.

Pain intensity

According to postoperative analgesic outcomes, at 6, 24, and 48 hours postoperatively, the VAS scores in the control and combination groups were 3.86 ± 0.19 and 2.24 ± 0.40, 2.67 ± 0.19 and 1.10 ± 0.23, and 1.79 ± 0.28 and 0.88 ± 0.16, respectively. The combination group showed significantly lower VAS scores at 6, 24, and 48 hours postoperatively than the control group (all P < 0.05, Figure 2).

Figure 2 Comparison of postoperative visual analog scale pain scores at 6, 24, and 48 hours postoperatively between the two groups. A: At 6 hours; B: At 24 hours; C: At 48 hours. ^cP < 0.0001. VAS: Visual analog scale.

Inflammatory factors

Comparison of inflammatory factors showed no notable differences in WBC count, NEUT%, and IL-6 levels between the groups preoperatively and 12 and 24 hours postoperatively (all P > 0.05). At 72 hours postoperatively, all measured indices in the combination group were significantly lower than those in the control group (WBC count: 9.8 ± 2.6 ×10⁹/L vs 10.5 ± 2.8 × 10⁹/L, NEUT%: 70.8 ± 5.9% vs 72.3 ± 6.2%, IL-6: 30.1 ± 14.2 pg/mL vs 35.2 ± 15.4 pg/mL) (all P < 0.05, Figure 3).

Figure 3 Comparison of white blood cell count, neutrophil percentage, and Interleukin-6 between the two groups preoperatively and 12, 24, and 72 hours postoperatively. A: White blood cell; B: Neutrophil percentage; C: Interleukin-6. ^aP < 0.05; ^cP < 0.0001. NS: Not significant; WBC: White blood cell; NEUT: Neutrophil; IL-6: Interleukin-6.

Blood gas analysis and metabolic status

Preoperatively, no significant inter-group differences were found in PaO₂, PaCO₂, or Lac levels (all P > 0.05). At 12 hours postoperatively, there was no significant difference in PaO₂ between both groups (P > 0.05). However, the combination group demonstrated significantly lower PaCO₂ (43.2 ± 3.8 mmHg vs 48.9 ± 4.1 mmHg, P < 0.001) and Lac concentration (1.9 ± 0.5 mmol/L vs 2.8 ± 0.6 mmol/L, P < 0.001) than the control group (Figure 4).

Figure 4 Comparison of partial pressure of O₂, partial pressure of CO₂, and lactate levels between the two groups preoperatively and 12 hours postoperatively. A: Partial pressure of O₂; B: Partial pressure of CO₂; C: Lactate. ^cP < 0.0001. NS: Not significant; PaO₂: Partial pressure of O₂; PaCO₂: Partial pressure of CO₂; Lac: Lactate.

Liver and kidney function

Preoperatively, the alanine aminotransferase, aspartate aminotransferase, serum creatinine, and blood urea nitrogen levels were similar between both groups (all P > 0.05). All indices showed a transient increase 24 hours postoperatively and decreased 72 hours postoperatively. However, at all time points, no significant inter-group differences were found in these indices (all P > 0.05, Figure 5).

Figure 5 Comparison of alanine aminotransferase, aspartate aminotransferase, serum creatinine, and blood urea nitrogen between the two groups preoperatively and 24 and 72 hours postoperatively. A: Alanine aminotransferase; B: Aspartate aminotransferase; C: Serum creatinine; D: Blood urea nitrogen. NS: Not significant; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; Cr: Creatinine; BUN: Blood urea nitrogen.

Complications

The combination group showed a significantly lower incidence of postoperative nausea and vomiting (PONV) than the control group (6/120, 5.0% vs 18/107, 16.8%; P = 0.004). There were no notable differences in other complications between the two groups, including pruritus (4/120, 3.3% vs 8/107, 7.5%; P = 0.144), respiratory depression (1/120, 0.8% vs 3/107, 2.8%; P = 0.343), or urinary retention (7/120, 5.8% vs 10/107, 9.3%; P = 0.311). The overall complication rate was notably lower rate was observed in the combination group than in the control group (17/120, 14.2% vs 33/107, 30.8%; P = 0.002, Table 2).

Table 2 Comparison of complications between the two groups, n (%).

	Control group (n = 107)	Combination group (n = 120)	χ2	P value
Postoperative nausea and vomiting	18 (16.8)	6 (5.0)	8.317	0.004
Pruritus	8 (7.5)	4 (3.3)	-	0.1441
Respiratory depression	3 (2.8)	1 (0.8)	-	0.3431
Urinary retention	10 (9.3)	7 (5.8)	1.025	0.311
Overall complications	33 (30.8)	17 (14.2)	9.333	0.002

¹Because of expected frequencies < 5, Fisher’s exact test was used to calculate the P value.

Multiple linear regression analysis of factors influencing postoperative pain

To identify the independent factors affecting postoperative pain, the VAS score at 24 hours postoperatively was adopted as the dependent variable, and the anesthesia method, IL-6 level 12 hours postoperatively, and Lac levels 12 hours postoperatively were included in the multiple linear regression model. The results (Table 3) identified anesthesia method as an independent influencing factor for the VAS score (β = -1.567, 95% confidence interval: -1.639 to -1.495, P < 0.001).

Table 3 Multiple linear regression analysis of factors influencing the visual analog scale score 24 hours postoperatively.

Factors	β	SD	Standardized coefficient β	t value	P value	95% confidence interval	Tolerance
Constant	2.695	0.094	-	28.698	< 0.001	2.510	2.880	2.695
Intervention methods	-1.567	0.036	-0.966	-43.089	< 0.001	-1.639	-1.495	-1.567
Postoperative IL-6	-0.001	0.001	-0.013	-0.781	0.435	-0.003	0.001	-0.001
Postoperative lactic acid	0.003	0.030	0.002	0.099	0.921	-0.056	0.062	0.003

IL-6: Interleukin-6.

DISCUSSION

LRG is the primary surgical approach for GC with relatively minimal trauma and reduced postoperative incisional pain. However, many patients may experience an internal environmental imbalance perioperatively, which hinders recovery[12,13]. This study systematically evaluated the efficacy of TPVB plus general anesthesia in older patients undergoing LRG for GC.

In this study, the combination group had significantly lower VAS scores at 6, 24, and 48 hours postoperatively than the control group. In the multiple linear regression model, the anesthesia method (i.e., whether combined with the TPVB) was identified as an independent factor that influenced the pain score. This finding is consistent with those of numerous domestic and international studies. For example, An et al[14] found that within the enhanced recovery after surgery pathway, TPVB plus general anesthesia effectively alleviated postoperative pain and accelerated recovery in older patients with lung cancer. Similarly, Wei et al[15] reported significantly lower postoperative VAS scores in older patients undergoing thoracoscopic lobectomy if TPVB was used for analgesia. The analgesic advantage of the TPVB stems primarily from its precise anatomical blocking mechanism, which involves injecting local anesthetics into the paravertebral space, thereby blocking conduction in the dorsal roots of the ipsilateral spinal nerve and communicating branches. This mechanism suppresses the transmission of nociceptive stimuli caused by surgical trauma to the central nervous system at its source[16,17]. This precise opioid-sparing mechanism is relevant as the participants were the older adults, a population often characterized by increased sensitivity to opioids[18].

Furthermore, although inflammatory markers increased in both groups at 12 and 24 hours postoperatively without significant differences, by 72 hours postoperatively, WBC count, NEUT%, and IL-6 levels were significantly lower in the combination group than in the control group. This may be because surgical trauma activates the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, triggering a strong neuroendocrine stress response and the release of large amounts of pro-inflammatory cytokines, leading to systemic inflammatory response syndrome[19,20]. This study observed significant intergroup differences in PaCO₂ and Lac levels, reflecting the positive impact of TPVB on patients’ physiological status. The significantly higher postoperative PaCO₂ in the control group suggests a higher degree of alveolar hypoventilation. This is commonly observed in older patients who avoid deep breathing and coughing because of incisional pain and an important predisposing factor for postoperative atelectasis and pulmonary infections[21]. The effective analgesia provided in the combination group helped preserve respiratory muscle function, enabling the patients to perform deep breathing and productive coughing, thereby maintaining alveolar ventilation and keeping PaCO₂ within a more favorable physiological range[9,22]. Blood Lac levels are sensitive indicators of tissue perfusion and oxygen metabolism[23]. The elevated postoperative Lac level in the control group may be attributed to pain-induced anxiety and tachycardia, which increase systemic oxygen consumption[24]. Contrastingly, TPVB provides effective analgesia, reduces opioid requirements, stabilizes sympathetic tone, optimizes the balance between oxygen supply and demand, and improves microcirculatory perfusion, thereby reducing the occurrence of anaerobic metabolism. Consequently, the combination group exhibited lower Lac concentrations[10].

The study results demonstrated that TPVB plus general anesthesia substantially reduced the incidence of PONV and overall complications. PONV is a common condition that prolongs hospital stay and decreases patient satisfaction, and its occurrence is strongly positively correlated with opioid dosage[25]. As the cornerstone of opioid-sparing strategies, TPVB fundamentally reduces this risk. Furthermore, the attenuated inflammatory stress, improved ventilation function, and lower Lac levels contribute to a more stable postoperative physiological state.

However, this study has limitations. First, as this was a single-center retrospective study, potential selection bias and unknown confounding factors may have existed. Second, the observation period was relatively short (72 hours postoperatively). Third, we did not precisely quantify the postoperative rescue opioid consumption. Fourth, the lack of significant differences in the liver and kidney function indices should be interpreted cautiously, as the small observed differences and wide variability may reflect insufficient statistical power; thus, false negatives cannot be excluded. Fifth, our exclusion criteria (ASA > II, BMI 18-27 kg/m², severe hepatic/renal dysfunction, and distant metastases) limited generalizability. Therefore, our findings are primarily applicable to relatively healthy, non-obese, non-metastatic older patients. Caution should be exercised in extrapolating these findings to a broader older GC population with more complex comorbidities or advanced disease stages. Future studies should investigate the role of the TPVB in these under-represented subgroups.

CONCLUSION

Overall, TPVB plus general anesthesia represents a safe and effective perioperative management strategy for older patients undergoing LRG for GC, providing significant analgesic benefits, alleviating inflammatory stress, improving respiratory function, and reducing postoperative complication rates.