Clinical Study of Stellate Ganglion Block Combined with General Anesthesia on Hemodynamics, Cognitive Function, and Gastrointestinal Function in Elderly Patients Undergoing Partial Hepatectomy

Abstract

Partial hepatectomy under general anesthesia is prone to hemodynamic alterations, and stress reactions are the main contributing factors to postoperative cognitive function in elderly partial hepatectomy patients. Postoperative cognitive dysfunction increases the incidence of postoperative complications and long-term morbidity and mortality in elderly patients. With the increasing trend of aging population and the gradual increase of elderly people undergoing surgical treatment, it is especially important to study the corresponding prevention and treatment measures. In this study, a total of 90 patients with primary liver cancer who received hepatectomy in our hospital from July 2020 to July 2021 were included as the research subject. The changes in hemorheology, stress-related indexes, cognitive function, postoperative pain, and gastrointestinal function were compared between the two groups The results showed that SGB combined with general anesthesia can effectively reduce hemodynamic fluctuations in elderly partial hepatectomy patients, alleviate surgical stress, promote postoperative recovery of cognitive function and gastrointestinal function with high safety, and is worthy of clinical promotion.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. Introduction

Primary hepatic carcinoma is one of the most common malignant tumors in human beings, and it is divided into hepatocellular carcinoma, cholangiocellular carcinoma, and mixed carcinoma according to pathological histology [1]. Primary hepatocellular carcinoma is prone to invade the branches of the portal vein and even block the main trunk of the portal vein [2]. Therefore, early intrahepatic metastasis is common and the prognosis of patients is poor. Partial hepatectomy is currently the first choice of effective treatment for primary liver cancer [3]. However, due to the effects of surgical trauma and organismal stress, most patients will suffer from postoperative complications such as pain, impaired organ function, and cognitive impairment [4]. With the increasing aging of the population, the incidence of primary liver cancer in the elderly and the number of elderly partial hepatectomy patients have increased compared with the previous ones. How to reduce the incidence of postoperative complications and improve the quality of life of patients has become a key issue in the treatment of elderly primary hepatocellular carcinoma.

Stellate ganglion block (SGB) is the injection of a local anesthetic into the loose connective tissue containing the stellate ganglion to achieve a reversible block of the cervical sympathetic trunk, cervical sympathetic ganglia with the preganglionic, postganglionic nerves, and their innervation territories [5, 6]. This method has been shown to inhibit pain, enhance hemodynamic stability, and reduce the adverse stress response caused by pituitary-adrenal seborrhea, with a high safety profile [7]. With the widespread promotion of SGB, its application value in elderly patients undergoing partial hepatectomy has generated heated debate. In this study, we analyzed the effects of SGB combined with general anesthesia on hemodynamics, postoperative cognitive function, and recovery of gastrointestinal function in elderly patients undergoing partial hepatectomy, which are reported below.

2. Materials and Methods

2.1. General Information

This study was a clinical randomized controlled trial. A total of 90 patients with primary liver cancer who received hepatectomy in our hospital from July 2020 to July 2021 were included as the research subject. Among them, 49 cases were male and 41 cases were female, with a mean age of (68.59 ± 2.38) years; 79 cases were hepatocellular carcinoma, 6 cases were cholangiocellular hepatocellular carcinoma, and 5 cases were mixed hepatocellular carcinoma. According to whether SGB was given or not, they were divided into SGB group and control group, 45 cases in each group.

2.2. Inclusion Criteria

(i) It was confirmed by pathological examination as primary hepatocellular carcinoma. (ii) All patients met the surgical indications [8] and had not undergone minimally invasive treatment or biological treatment for hepatocellular carcinoma before enrollment. (iii) All patients were first-time patients; all signed the informed consent form.

2.3. Exclusion Criteria

(i) Patients with coagulation disorders; (ii) patients with severe cerebrovascular diseases, endocrine system diseases, psychiatric diseases, and severe gastrointestinal insufficiency; (iii) patients with more than 3 intrahepatic lesions; and (iv) patients with negative Horner syndrome after SGB.

2.4. Method

Intravenous access was established to maintain electrolyte and acid-base balance in both groups. All patients underwent laparoscopic regular partial hepatectomy under general anesthesia. In the SGB group, SonoSite Edge II Ultrasound system (Fujifilm, Japan) was used 15 min before induction of anesthesia, and the probe frequency was set to 10 MHz.

The probe was placed perpendicular to the right sternocleidomastoid muscle, and the position of the anterior and posterior nodes of the C6 transverse process, the C6 nerve root, and the long cervical muscle where the vertebral body and the root of the C6 transverse process form an oval shape was determined, and the angle of the probe was adjusted to make an angle of 45°with the sagittal plane of the neck. The carotid artery sheath is dissected outward, and the needle is inserted perpendicular to the cricoid cartilage to the cervicalis longus muscle at the root of the C6 transverse process. When cerebrospinal fluid, blood, and gas were not pumped back, 8 mL of 1% lidocaine was injected into the root of the right C6 transverse tubercle for SGB.

Effective signs of SGB: Horner syndrome appeared on the block side, namely, small right fissure, ptosis, constricted pupil, eyeball retraction, facial perspiration, etc. Induction of anesthesia: midazolam 0.04 mg/kg, sufentanil 0.3 μg/kg, atracurium 0.8 mg/kg, propofol 0.8 mg/kg, target-controlled infusion (plasma concentration) of remifentanil 1 to 2 ng/mL, propofol 2 to 3 μg/mL, inhalation of sevoflurane 1% + oxygen 2 L/min to maintain anesthesia, intraoperative BIS 45 to 55. Atracurium 0.3 mg/kg was injected intravenously every 40 min, and sevoflurane inhalation was stopped 30 min before the end of surgery. The patients were discharged back to the ward after their uneventful vital signs and the Steward score ≥4.

The control group was operated as the SGB group except that SGB was not used.

2.5. Observation Indexes

2.5.1. Hemodynamics

3 mL peripheral blood was collected at five time points, including before tracheal intubation, immediately after tracheal intubation, immediately after the establishment of pneumoperitoneum, immediately after partial hepatectomy, and immediately after extubation; then centrifuged (1500 r/min, 15 min), separated and processed, and sent for examination; and the mean arterial pressure (MAP) and heart rate (HR) were measured by chemical contrast staining.

2.5.2. Oxidative Stress Response

Before anesthesia, 1 hour after cuts in the skin, suturing after operation, and 24 h after surgery, 10 mL of fasting blood samples were collected from all patients, and the supernatant was collected by centrifugation (3000 r/min, 10 min). The levels of cortisol (Cor) and adrenaline (A) were measured by hormone immunoassay, and the levels of interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay.

2.5.3. Cognitive Function

The Loewenstein cognitive function assessment scale (LOTCA) [9] was used to assess the cognitive function of patients 1 d before surgery and 1, 3, and 7 d postoperatively. The score includes cognitive function, speech, memory, motor, and visuospatial skills. The total score was 100 points, and the lower the score, the better the cognitive function.

2.5.4. Analgesic Effect

The visual analogue score (VAS) [10] was used to assess the postoperative pain level at 6, 12, 24, and 48 h postoperatively, with a total score of 10, with ≤3 being mild pain, 4–6 being moderate pain, and >6 being severe pain.

2.5.5. Recovery of Gastrointestinal Function

The postoperative abdominal pain relief time, postoperative bowel sound disappearance time, and postoperative anal recovery time between the two groups were compared.

2.5.6. Adverse Reactions

All patients’ postoperative complications, which include bradycardia, hypotension, respiratory depression, nausea, and vomiting, were observed.

2.6. Statistical Methods

All data were processed with SPSS 22.0 statistical software, and GraphPad Prism 8 was used to make statistical graphs. Measurement data are expressed as mean ± standard deviation ($\overline{x}\pm s$), an independent sample t-test is used for comparison between groups, count data are expressed as [n (%)], and the chi-square (χ²) test is performed. The difference is statistically significant when $P<0.05$.

3. Results

3.1. Comparison of General Data between the Two Groups

There was no difference in general data between the two groups ($P>0.05$, Table 1).

Table 1

Comparison of general data between the two groups.

Group	Average age	Gender		Pathological types			ASA grading
		Male	Female	Hepatocellular carcinoma	Cholangiocellular carcinoma	Mixed hepatocellular carcinoma	I	II
SGB group (n = 45)	68.32 ± 2.41	25	20	40	4	1	29	16
Control group (n = 45)	68.71 ± 2.39	24	21	39	2	4	31	14
t/χ2	0.771	0.045		2.479			0.200
$P$	0.443	0.832		0.289			0.655

3.2. Comparison of Changes in Hemodynamic Indexes before and after Anesthesia in the Two Groups

The HR and MAP levels immediately after tracheal intubation, immediately after the establishment of pneumoperitoneum, immediately after partial hepatectomy, and immediately after extubation were all higher than those before tracheal intubation ($P<0.05$). Meanwhile, the HR immediately after tracheal intubation, immediately after establishment of pneumoperitoneum, immediately after partial hepatectomy, and immediately after extubation were lower in the SGB group than in the control group, and the MAP levels at the time points immediately after tracheal intubation and immediately after establishment of pneumoperitoneum were lower in the SGB group than in the control group ($P<0.05$, Table 2).

Table 2

Comparison of changes in hemodynamic indexes before and after anesthesia in the two groups ($\overline{x}\pm s$).

Indicators		Before tracheal intubation	Immediately after tracheal intubation	Immediately after the establishment of pneumoperitoneum	Immediately after hepatectomy	Immediately after extubation	F	$P$
HR (times/min)	SGB group (n = 45)	73.16 ± 6.39	75.32 ± 7.48	77.31 ± 6.52	81.37 ± 4.11	76.34 ± 5.36	11.18	≤0.001
	Control group (n = 45)	73.95 ± 6.14	79.17 ± 7.34	81.09 ± 6.71	84.98 ± 5.36	79.36 ± 5.84	17.84	≤0.001
	t	0.598	2.464	2.710	3.585	2.556	—	—
	$P$	0.551	0.016	0.008	0.001	0.012	—	—
MAP (mmHg)	SGB group (n = 45)	87.49 ± 6.58	89.31 ± 6.17	92.39 ± 6.74	95.23 ± 5.11	89.46 ± 5.43	11.45	≤0.001
	Control group (n = 45)	88.25 ± 6.31	91.94 ± 6.45	96.18 ± 5.83	101.30 ± 4.36	90.44 ± 6.17	34.99	≤0.001
	t	0.559	1.977	2.853	6.062	0.800	—	—
	$P$	0.577	0.051	0.005	≤0.001	0.426	—	—

3.3. Comparison of Changes in Oxidative Stress Indexes before and after Anesthesia between the Two Groups

Compared with the basal values before anesthesia, the peripheral blood Cor, A, and IL-6 levels were significantly higher in both the control group and the SGB group at 1 hour after cuts in the skin and suturing after operation ($P<0.05$), while they gradually returned to the preanesthesia levels at 24 h after surgery, the peripheral blood Cor, A, and IL-6 levels were lower in the SGB group than in the control group at 1 hour after cuts in the skin and suturing after operation, and the two groups compared to the control group with statistical significance ($P<0.05$, Table 3).

Table 3

Comparison of changes in oxidative stress indexes before and after anesthesia between the two groups ($\overline{x}\pm s$).

Indicators		Before anesthesia	1 hour after cuts in the skin	Suturing after operation	24 h after surgery	F	$P$
Cor (mmol/L)	SGB group (n = 45)	196.31 ± 16.39	205.49 ± 18.41	227.36 ± 17.68	204.66 ± 18.69	24.96	≤0.001
	Control group (n = 45)	195.87 ± 16.14	223.34 ± 18.14	246.54 ± 18.31	205.09 ± 18.73	70.51	≤0.001
	T	0.128	4.633	5.055	0.109	—	—
	$P$	0.898	≤0.001	≤0.001	0.913	—	—
A (ng/mL)	SGB group (n = 45)	126.59 ± 16.09	137.84 ± 17.11	145.32 ± 16.98	127.66 ± 16.02	12.99	≤0.001
	Control group (n = 45)	125.34 ± 16.44	146.05 ± 18.42	154.25 ± 17.44	126.33 ± 16.21	25.87	≤0.001
	T	0.365	2.191	2.461	0.392	—	—
	$P$	0.716	0.031	0.016	0.696	—	—
IL-6 (μg/L)	SGB group (n = 45)	60.39 ± 6.25	65.74 ± 7.13	71.33 ± 6.59	71.02 ± 6.35	21.53	≤0.001
	Control group (n = 45)	60.44 ± 6.34	72.63 ± 7.84	79.66 ± 8.46	71.13 ± 6.49	40.99	≤0.001
	T	0.033	3.846	4.96	0.072	—	—
	$P$	0.974	≤0.001	≤0.001	0.943	—	—

3.4. Comparison of LOTCA Scores before and after Surgery between the Two Groups

The LOTCA scores of 1 d and 3 d postoperatively were higher than those of preoperative and 7 d postoperatively in both groups ($P<0.05$); there was no difference between the LOTCA scores of preoperative and 7 d postoperatively in both groups, and the LOTCA scores of 1 d and 3 d postoperatively in the SGB group were lower than those of the control group ($P<0.05$, Table 4 and Figure 1).

Table 4

Comparison of LOTCA scores before and after surgery between the two groups ($\overline{x}\pm s$, score).

Group	1 d before surgery	1 d postoperative	3 d postoperative	7 d postoperative	F	$P$
SGB group (n = 45)	79.36 ± 10.32	69.44 ± 10.41	61.39 ± 13.59	54.65 ± 10.64	30.96	≤0.001
Control group (n = 45)	79.13 ± 10.85	75.06 ± 10.52	68.18 ± 12.63	60.26 ± 9.76	19.84	≤0.001
t	0.091	2.247	2.165	2.299	—	—
$P$	0.928	0.028	0.034	0.025	—	—

[figure omitted; refer to PDF]

3.5. Comparison of Postoperative VAS Scores between the Two Groups

The postoperative VAS scores in both groups showed a decreasing trend and reached the lowest value at 48 h postoperatively. 6-h, 12-h, and 24-h postoperative VAS scores in the SGB group were lower than those in the control group ($P<0.05$), but there was no statistical significance in the comparison of the 48-h postoperative VAS scores between the two groups ($P>0.05$, Table 5).

Table 5

Comparison of postoperative VAS scores between the two groups ($\overline{x}\pm s$, score).

Group	6 h postoperative	12 h postoperative	24 h postoperative	48 h postoperative	F	$P$
SGB group (n = 45)	6.54 ± 1.32	5.03 ± 1.16	4.19 ± 1.05	2.59 ± 0.66	105.78	≤0.001
Control group (n = 45)	6.51 ± 1.39	5.84 ± 1.32	4.85 ± 1.16	2.64 ± 0.68	93.80	≤0.001
T	0.093	2.727	2.496	0.312	—	—
$P$	0.927	0.008	0.015	0.756	—	—

3.6. Comparison of Postoperative Recovery of Gastrointestinal Function between the Two Groups

Compared with the control group, abdominal pain relief time, bowel sound disappearance time, and recovery time of anal exhaust were shorter in the SGB group ($P<0.05$, Table 6).

Table 6

Comparison of the improvement of gastrointestinal function between the two groups of patients ($\overline{x}\pm s$).

Group	Abdominal pain relief time (h)	Bowel sound disappearance time (h)	Recovery time of anal exhaust (h)
SGB group (n = 45)	27.69 ± 4.21	25.11 ± 2.36	32.96 ± 5.16
Control group (n = 45)	35.11 ± 4.84	33.05 ± 2.15	40.11 ± 5.12
t	6.843	14.714	5.819
$P$	≤0.001	≤0.001	≤0.001

3.7. Comparison of Adverse Reactions between the Two Groups

The incidence of adverse reactions in the SGB group was 8.89%, and the incidence of adverse reactions in the control group was 6.67%. The comparison of the incidence of adverse reactions between the two groups was not statistically significant ($P>0.05$, Table 7).

Table 7

Comparison of the occurrence of adverse reactions in the two groups [n (%)].

Group	Bradycardia	Hypotension	Respiratory depression	Nausea and vomiting	Total
SGB group (n = 45)	2 (4.44)	1 (2.22)	0 (0.00)	1 (2.22)	4 (8.89)
Control group (n = 45)	1 (2.22)	1 (2.22)	0 (0.00)	1 (2.22)	3 (6.67)
χ2					0.155
$P$					0.694

4. Discussion

The stellate ganglion is centrally located at the level of the 1st rib neck at the top of the pleura and is formed by the fusion of the inferior cervical ganglion and the T1 ganglion [11]. Stellate ganglion receives the upper thoracic preganglionic sympathetic nerve fibers uploaded along the sympathetic nerve chain [12]. After exchanging neurons, the stellate ganglion can send out the postganglionic nerve fibers, which are used to innervate the head, neck, upper limb, chest heart, and other organ tissues [13]. Currently, SGB has been increasingly used in clinics as a treatment for pain diseases.

Partial hepatectomy under general anesthesia is prone to violent hemodynamic fluctuations, which can increase the risk of anesthesia and cause surgical accidents [14]. SGB can block the sympathetic nerve leading to the head, neck, upper limb, heart, and lung, thus blocking the excitatory conduction of sympathetic nerves and the release of vasoactive substances, which in turn reduces the stress response [15]. At the same time, it can effectively inhibit blood pressure fluctuation and arrhythmia, thus alleviating the cardiovascular response during intubation and extubation [16, 17]. Tracheal intubation, pneumoperitoneum establishment, and extubation are the time points that cause intraoperative hemodynamic fluctuations in patients undergoing laparoscopic surgery [18]. The results of this study showed that the HR and MAP levels were significantly higher in both groups from the immediate post-tracheal intubation period, confirming that tracheal intubation caused dramatic hemodynamic fluctuations in the organism. However, the HR level in the SGB group was lower than that in the control group at any time point from immediately after tracheal intubation to immediately after extubation, and the MAP level at the time points immediately after tracheal intubation and immediately after pneumoperitoneum establishment was lower than that in control group ($P<0.05$). These results indicate that SGB has a certain inhibitory effect on the cardiovascular reactions caused by irritating operations during anesthesia in elderly patients undergoing partial hepatectomy and can effectively reduce the fluctuations of hemodynamics.

The stress response refers to the individual nonspecific response caused by various stressors, and its physiological responses are manifested by sympathetic nerve excitation, increased secretion of pituitary and adrenocortical hormones, elevated blood glucose, elevated blood pressure, increased heart rate, and accelerated respiration [19]. Cor has important functions in the manipulation of mood and health, immune cells, and the link between inflammation, blood vessels, and blood pressure. Under stressful conditions, Cor generally keeps the blood pressure stable and controls excessive inflammatory reaction [20]. A is a hormone and neurotransmitter released by adrenal gland. Il-6 can induce the differentiation of B cells and the production of antibodies and induce the activation of proliferation and differentiation of T cells [21]. And it participates in the body’s immune response, which can promote the development of inflammatory responses. Operation and postoperative pain are strong stressors. The results of this study showed that compared with the basal values before anesthesia, the peripheral blood Cor, A, and IL-6 levels were significantly higher in both the control group and the SGB group at 1 hour after cuts in the skin and suturing after operation ($P<0.05$). SGB can inhibit the release of norepinephrine, Cor, and angiotensin II through the HPA axis, thus stabilizing the internal environment of the body, maintaining the stability of immune function, endocrine function, and circulatory function, and achieving the purpose of inhibiting the stress response. In this study, the peripheral blood Cor, A, and IL-6 levels were lower in the SGB group than in the control group at 1 hour after cuts in the skin and suturing after operation ($P<0.05$), which indicated that SGB could effectively relieve the surgical stress reaction of elderly patients undergoing partial hepatectomy.

Postoperative cognitive dysfunction (POCD) is a frequent complication of surgical procedures [22]. The mechanism of POCD is not completely clear, but pain, stress response, blood pressure fluctuation, and the anesthesia method are closely related to it. Abnormal cerebral oxygen metabolism is an important contributor to POCD [23]. SGB can relieve intracranial vasospasm, dilate blood vessels, improve cerebrovascular circulation, and ensure blood oxygen supply in brain tissue [24]. At the same time, it can regulate endocrine and neurological fluids, coordinate systemic organ functions, promote the recovery of physiological functions of the body, and relieve neurological symptoms of postoperative patients [25]. LOTCA is a kind of cognitive function scale that is used more frequently abroad, which can comprehensively evaluate memory, attention, recall, language, visuomotor organization, spatial perception, and thinking of patients [26]. In this study, the LOTCA scores of the SGB group were lower at 1 d and 3 d after surgery than those of the control group ($P<0.05$). These results indicate that SGB is helpful to the postoperative recovery of cognitive function and reduce the risk of POCD in elderly patients undergoing partial hepatectomy.

Elderly patients after partial hepatectomy are prone to gastrointestinal dysfunction, which will not only prolong food intake time but also lead to decreased immune function of the body, causing complications such as intestinal adhesion, anastomotic leakage, and enterogenous infection. Preoperative SGB can effectively inhibit the body’s stress response and inflammatory response to abdominal surgical trauma, thereby promoting the recovery of postoperative gastrointestinal motility. In this study, compared with the control group, the postoperative relief time of abdominal pain, postoperative disappearance time of bowel sound, and postoperative recovery time of anal exhaust were shorter in the SGB group ($P<0.05$),indicating that SGB can promote postoperative gastrointestinal function recovery in surgical elderly partial hepatectomy patients. In addition, the investigation of adverse reactions showed that there was no difference in the rate of adverse reactions between the two groups. Ultrasound-guided SGB can better display the soft tissue structures around the SG, locate the needle tip position, achieve the purpose of reducing the damage to adjacent organs and tissues, improve the success rate of block, and dynamically observe the puncture needle travel and drug diffusion in real time [27]. Therefore, the safety and efficacy of SGB are worthy of affirmation.

To summarize, SGB combined with general anesthesia can effectively reduce hemodynamic fluctuations in elderly partial hepatectomy patients, alleviate surgical stress, promote postoperative recovery of cognitive function and gastrointestinal function with high safety, and is worthy of clinical promotion.

Ethical Approval

This study was approved by the Ethics Committee of Yuebei People’s Hospital Affiliated to Shantou University Medical College, the 908th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force, and Huazhong University of Science and Technology Union Shenzhen Hospital.

Disclosure

Wen Chen and Baohua Chen are the first coauthors of the paper.

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