Effect of nalbuphine on analgesia and pain factors after gastric cancer resection

Abstract

BACKGROUND

Gastric cancer (GC) is a prevalent tumor in the digestive system, with around one million new cases reported annually, ranking it as the third most common malignancy. Reducing pain is a key research focus. This study evaluates the effect of nalbuphine on the analgesic effect and the expression of pain factors in patients after radical resection.

AIM

To provide a reference for postoperative analgesia methods.

METHODS

One hundred eight patients with GC, admitted between January 2022 and June 2024, underwent radical gastrectomy. They received a controlled analgesia pump and a transverse abdominis muscle plane block, divided into two groups of 54 patients in each group. The control group received sufentanil, while the observation group received nalbuphine as an analgesic. Postoperative analgesic effects, pain factor expression, and adverse effects were compared.

RESULTS

The resting pain and activity pain scores in the observation group at 6, 12, 24 and 48 hours were significantly lower than those in the control group. Additionally, the number of presses and consumption of the observation group at 48 hours were lower than those of the control group; and the response rate of the observation group was higher than that of the control group (P < 0.05). The prostaglandin E2, substance P, and serotonin levels 24 hours after the observation group were lower than those in the control group, and the incidence of adverse reactions was 5.56% lower than 22.22% in the control group (P < 0.05).

CONCLUSION

The findings suggest that nalbuphine enhances postoperative multimodal analgesia in patients with radical GC, effectively improving postoperative analgesic effect, relieving postoperative resting and active pain, and reducing postoperative pain factor expression, demonstrating its potential for clinical application.

Key Words: Nalbuphine; Radical resection of gastric cancer; Multimodal analgesia; Clinical treatment; Tumor

Core Tip: Nalbuphine, recognized for its potent analgesic properties, plays a crucial role in significantly enhancing postoperative pain management for patients who have undergone radical gastrectomy. Nalbuphine stands out due to its lower frequency of adverse reactions compared to other analgesics, which is a significant advantage in clinical settings. This lower incidence of side effects, coupled with its efficacy, positions nalbuphine as a promising candidate for improving patient recovery and overall comfort in the postoperative period, potentially leading to better patient outcomes and satisfaction.

INTRODUCTION

Gastric cancer (GC) is a prevalent tumor of the digestive system, with an estimated one million new cases reported each year, and its incidence is the third of all malignancies[1]. Surgical resection combined with peripheral lymph node dissection is the preferred treatment for GC; however, postoperative incision pain, visceral pain, and other conditions affect the postoperative rehabilitation level and prolong hospital stay[2]. Therefore, the clinical focus is on selecting a reasonable and effective analgesic plan to reduce postoperative pain degree of patients and promote postoperative rehabilitation. Currently, multimodal analgesia is used for patients undergoing radical gastrectomy, with a nerve block combined with an automatic analgesia pump as the main method. In the process of intravenously controlled analgesia, sufentanyl, which has a prominent central analgesic effect, is most commonly selected[3]. However, when sufentanyl is used alone, its adverse effects are dose-dependent, and long-term and high-dose applications can easily increase postoperative adverse effects, which affect the postoperative rehabilitation of patients[4]. Therefore, choosing a safer and more effective analgesic agent is necessary. Nabphine is a novel opioid receptor agonist/antagonist whose analgesic intensity is highly consistent with that of morphine, and it has specific effects on somatic surface pain and visceral pain[5]. At this time, it is worth exploring whether nalbuphine can be used for multimodal analgesia after radical resection. Based on this, this study analyzed the effect of nabphine on the analgesic effect and expression of pain factors in patients with multimodal analgesia after radical resection. It aimed to provide a reference for postoperative analgesia methods. Compared to other opioid or non-opioid analgesics, nalbuphine exhibits analgesic efficacy equivalent to that of morphine, offering improved tolerability and safety in specific scenarios[6]. The side effects of nalbuphine are generally fewer than those of full-agonist opioids, particularly respiratory depression and constipation[7]. Furthermore, the potential for nalbuphine dependence and abuse is generally lower than that of full-agonist opioids, which may render it a safer alternative[8].

MATERIALS AND METHODS

General information

This study selected 108 patients who were admitted to the hospital from January 2022 to June 2024, and underwent radical gastrectomy. The patients were divided into two groups according to the random number table method. The control group consisted 54 patients, including 28 men and 26 women, with an age range of 35-78 (62.79 ± 4.15) years old. Tumor classification revealed 32 cases of adenocarcinoma and 22 cases of squamous cell carcinoma. Surgical procedures included 36 laparoscopic procedures and 18 cases of open abdominal surgery. According to the Association of Anesthesiologists (ASA) classification, there were 12 patients classified as grade I, 34 as grade II, and eight as grade I. In terms of tumor-node-metastasis staging, there were 20 cases in stage I, period of 34 cases. The operation time ranged from 142-268 (192.48 ± 21.07) minutes. Of the 54 patients, comprising 31 men and 23 women cases, with ages ranging from 35 to 78 (63.08 ± 4.28). Tumor classification showed 30 cases of adenocarcinoma, and 24 cases of squamous cell carcinoma. Surgical procedures included 33 laparoscopic procedures, and 21 cases of laparotomy. According to ASA classification there were 10 patients of grade I, 35 patients of grade II and nine patients of grade III. In terms of tumor-node-metastasis staging, there were 17 cases in stage I and 37 cases in stage II. The operation time ranged from 140 to 275 (194.19 ± 22.26) minutes. Comparison of baseline data in the two groups (P < 0.05), comparable.

Ranking standard

The inclusion criteria were as follows: (1) All enrolled patients met the GC criteria[9]; (2) Indications for radical gastric resection; (3) Anesthesia ASA grade I; and (4) Informed study and signed consent form. The exclusion criteria were as follows: (1) Other organic diseases; (2) History of opioid dependence and abuse; (3) History of chronic pain diseases; (4) Recent history of sedatives, antidepressants, and analgesic drugs; (5) Cognitive impairment and mental abnormalities; and (6) History of anesthetic allergy.

In both groups, the transverse abdominis plane block was used, the needle was inserted into the lower transverse abdominis plane under the bilateral costal edge, and 20 mL of 0.25% ropivacaine (Jiangsu Hausen Pharmaceutical, Chinese drug-approved H20060136) was injected. At the same time, postoperative automatic analgesia pump. In the control group, sufentanil was used as analgesic drug, that is, sufentanil (Yichang Renfu Pharmaceutical, H20050580) 150 μg + granisetron (Chengdu Pushe, H20055815 H20055815) was diluted to 120 mL. In the observation group, nalbuphine was selected; that is, nalbuphine (Yichang Renfu Pharmaceutical, Chinese drug approved H20130127) 1 mg/kg + granisetron 3 mg + normal saline was diluted to 120 mL. The analgesia pump parameters were as follows: A continuous dose of 2.5 mL per hour, a controlled dose of 2 mL/hour, and a locking time of 15 minutes.

Observations

Postoperative pain degree: (1) The degree of postoperative pain was evaluated at 1, 6, 12, 24, 48 hours, using the numerical grade scoring method[10] which assesses pain levels at rest and during activities (such as cough, turning over and other movements). The scale ranges from 0 to 10, with higher scores indicating greater pain intensity; (2) Analgesic effect: The postoperative analgesic efficiency, the number of presses and consumption in 48 hours after surgery were recorded; (3) Pain-related factors level: 5 mL of peripheral venous blood was collected before and 24 hours after surgery. The samples were centrifuged for 10 minutes at 3000 rpm to obtain upper serum. The levels of prostaglandin E2 (PGE2), substance P (SP) and serotonin (5-HT) were measured by enzyme-linked immunoassay; and (4) Adverse reactions: The occurrence of adverse reactions including nausea, vomiting, respiratory depression, urinary retention, dizziness, and drowsiness was monitored throughout the postoperative period.

Statistical analysis

SPSS26.0 Statistics software processed the data. Data normality was tested using a Q-Q plot. Measurement data that followed a normal distribution were expressed as mean ± SD, and analyzed using independent and paired sample t-tests. Categorical data were expressed as rates (%), and analyzed using χ² test; P < 0.05 is statistically significant.

RESULTS

The degree of pain

The resting pain and activity pain scores of the observation group at 6, 12, 24, and 48 hours were lower than those of the control group. The number of presses and consumption of the observation group at 48 hours were lower than those of the control group, and the response rate of the observation group was higher than that of the control group (P < 0.05), as shown in Table 1.

Table 1 Comparison of pain levels between the two groups (score, mean ± SD).

Group	Status	1 hour after surgery	6 hours after surgery	12 hours after surgery	24 hours after surgery	48 hours after surgery
Observation (n = 54)	Tranquillization	1.42 ± 0.36	2.36 ± 0.41a	3.15 ± 0.48a	3.07 ± 0.50a	2.48 ± 0.46a
	Activity	1.96 ± 0.41	3.18 ± 0.42a	4.82 ± 0.56a	4.73 ± 0.63a	3.01 ± 0.64a
Control (n = 54)	Tranquillization	1.45 ± 0.38	3.17 ± 0.48	4.20 ± 0.51	4.08 ± 0.58	3.27 ± 0.51
	Activity	2.01 ± 0.48	4.18 ± 0.50	5.86 ± 0.67	5.96 ± 0.72	4.16 ± 0.82

^aP < 0.05, compared with the control group in the same state.

Analgesia effect

The number of presses and consumption in the observation group was lower than those in the control group, whereas the response rate was higher than that in the control group (P < 0.05), as shown in Table 2.

Table 2 Comparison of the analgesic effects between the two groups (mean ± SD).

Group	48 hours presses (times)	48-hour consumption (mL)	Effective percentage (%)
Observation (n = 54)	2.84 ± 0.71	18.28 ± 2.48	75.28 ± 3.15
Control (n = 54)	4.73 ± 0.69	35.48 ± 3.69	70.04 ± 3.06
t	14.028	28.429	8.768
P value	< 0.001	< 0.001	< 0.001

Pain-related factors

The expression of pain-related factors was compared between the two groups before surgery (P < 0.05), and the expression of PGE2, SP, and 5-HT in the observation group at 24 hours was lower than that in the control group (P < 0.05; Table 3).

Table 3 Comparison of pain-related factor expression between the two groups (mean ± SD).

Group	PGE2 (pg/mL)		5-HT (ng/mL)		SP (μg/mL)
	Preoperative	24 hours after surgery	Preoperative	24 hours after surgery	Preoperative	24 hours after surgery
Observation (n = 54)	98.82 ± 12.07	138.84 ± 15.61a	121.28 ± 26.36	178.82 ± 31.35a	0.80 ± 0.21	1.48 ± 0.23a
Control (n = 54)	101.06 ± 15.63	169.86 ± 18.82a	118.84 ± 27.49	226.81 ± 36.71a	0.79 ± 0.20	1.96 ± 0.34a
t	0.834	9.323	0.471	7.305	0.253	8.593
P value	0.406	< 0.001	0.639	< 0.001	0.800	< 0.001

^aP < 0.05, compared with the preoperative procedure.

PGE2: Prostaglandin E2; 5-HT: Serotonin; SP: Substance P.

Untoward effect

The incidence of postoperative adverse effects in the observation group was lower than in the control group (P < 0.05; Table 4).

Table 4 Comparison of adverse reactions between the two groups, n (%).

Group	Nausea and vomitting	Shiver	Dizzy	Drowsiness	Retention of urine	Respiratory depression	Total
Observation (n = 54)	1 (1.85)	0	1 (1.85)	1 (1.85)	0	0	3 (5.56)
Control (n = 54)	3 (5.56)	2 (3.70)	2 (3.70)	2 (3.70)	1 (1.85)	2 (3.70)	12 (22.22)
χ2							6.271
P value							0.012

DISCUSSION

Surgery is the preferred method for cancer, which can remove the primary lesion of the tumor significantly and reduce the risk of death. In recent years, with the continuous improvement in the prevalence of GC, the level of radical resection of GC has significantly improved; however, postoperative pain is the primary factor affecting the rehabilitation effect of patients. As intraoperative wound cutting, organ resection, visceral pulling, and other operations can induce incision pain, visceral pain, and inflammatory pain, many patients experience moderate to severe postoperative pain, strong stress reactions, aggravated postoperative immune suppression, and increased risk of postoperative infection[11]. Therefore, postoperative pain management should be the focus of postoperative surgical attention.

Currently, multimodal analgesia using an automatic analgesia pump combined with nerve block technology is significantly used for patients with radical GC. Nerve block technology can inject a local anesthetic drug into the fascia layer of the nerve area in the abdomen so that the drug solution can spread to the target nerve and play an analgesic role[12]. As the analgesic effect of nerve block technology is affected by the duration of local anesthesia, the analgesic effect in some patients gradually declines shortly after surgery. At this time, a multi-controlled analgesic pump can provide sustained analgesia, providing a lasting and long-term analgesic effect[13]. Among them, sufentanil is a commonly used analgesic drug with high-fat solubility, easy to cross the blood-brain barrier, and small distribution volume, which can antagonize the mu opioid receptor in the nociceptive conduction area and play an analgesic effect. However, if the background dose is applied when sufentanil is significantly high, adverse reactions can occur, whereas a low dose leads to a poor analgesic effect in patients[14]. The analgesic effect of nalbuphine has been clinically recognized; it can significantly reduce moderate to severe pain and has a “capping effect”, outdated dosage, and no noticeable side effects[7]. This study showed that the resting pain and activity pain scores at 6, 12, 24, and 48 hours were lower than those of the control group; the number of presses and consumption at 48 hours after surgery were lower than those of the control group; and the response rate was higher than that of the control group (P < 0.05). This indicates that, compared with sufentanil, nalbuphine has a better analgesic effect and can reduce the number of presses on the analgesic pump and the consumption of analgesics. Deslandes et al[6] noted that compared with morphine, nalbuphine provides better analgesia and has a lower complication rate. Sufentanil primarily acts on mu opioid receptors to exert an analgesic effect, but it has a poor effect on visceral pain caused by intraoperative pain, spasms, and ischemia[15].

Central sensitization is an important mechanism that induces pain when the central nervous system amplifies pain signals. PGE2 can promote pain sensitivity and reduce the body’s pain threshold. The higher the expression, the more pronounced the pain in the body. 5-HT can transmit pain signals and pain stimuli to the central nervous system. SP is an important factor that reflects the degree of pain, and its expression is proportional to the degree of pain[16]. The present study showed that the levels of pain factors at 24 hours in the observation group were lower than those in the control group (P < 0.05). This indicates that nalbuphine significantly reduces the expression of pain sensitization factors, thereby exerting a significant analgesic effect.

Regarding drug safety, adverse effects were lower in the observation group of 5.56%, lower than 22.22% in the control group (P < 0.05). He et al[8] showed that using nalbuphine in children who underwent adenoid tonsillectomy, the incidence of agitation (10.28%) was significantly lower than that in the saline group (28.39%), and 33.58% of moderate to severe pain was lower than that in the saline group (60.5%; P < 0.05). Wang et al[17] showed that prophylactic intravenous nalbuphine could reduce the effective dose of pain by half after a laparoscopic total hysterectomy. In contrast, the incidence of adverse events was comparable to 24 hours after nalbuphine. The results show that nabphine for analgesia has fewer adverse effects and higher safety. Sufentanil is primarily a simple opioid mu receptor agonist, which has no pronounced effect on visceral pain. To exert an analgesic effect, the drug dose is constantly increased, and the postoperative analgesia time for patients with gastric GC is long. With the accumulation of sufentanil, the incidence of adverse reactions has significantly increased. Nalbuphine not only has the effect of mu receptor but also acts on κ receptor to reduce the excitability of neurons and mechanosensory neurons, thus relieving postoperative visceral pain, reducing the dosage of analgesic drugs, and controlling the occurrence of postoperative adverse reactions. At the same time, nalbuphine has low dependence and fewer side effects, which can antagonize μ receptor and reduce the adverse reactions of excited mu receptor, with higher safety.

CONCLUSION

In conclusion, using nabphine for postoperative multimodal analgesia in patients with radical GC can improve the postoperative analgesic effect, relieve postoperative resting and active pain, reduce the expression of postoperative pain factors, and reduce the incidence of postoperative adverse reactions, with high safety and suitability for visceral pain. However, this study had a small sample size, more postoperative analgesic measures, and many confounding factors, which could easily lead to outcome bias. Therefore, multicenter studies with large sample sizes are needed to reduce the influence of confounding factors and clarify the analgesic effect of nalbuphine.