Anesthetic Effect of Dexmedetomidine in Clinical Functional Neurosurgery.

Background: Dexmedetomidine is a highly selective and efficient α2-adrenoceptor agonist with good antianxiety, analgesic, hypnotic, and sedative effects without causing respiratory depression. Aim: To investigate the anesthetic effect of dexmedetomidine in clinical neurosurgery.
Methods: A total of 94 patients who received functional neurosurgical treatment in our hospital from March 2019 to October 2020 were selected and divided into the study and control groups. Routine anesthesia was adopted in the control group, while dexmedetomidine was used in the study group. Perioperative hemodynamic indicators such as mean arterial pressure, heart rate, and peripheral capillary oxygen saturation, cognitive function score, pain score VAS, stress response index level, and incidence of adverse reactions were compared between the two groups.
Results: Before surgery (T0), no significant differences in MAP, HR, and SpO2 were observed between the two groups. However, at the beginning of the operation (T1), 30 min after the operation (T2), and immediately after the operation (T3), these indicators in the study group were significantly higher than in the control group. The postoperative MMSE of the study group 3 d later was significantly higher than that of the control group. The VAS scores after the operation of the study group were lower than those of the control group. The serum cortisol (COR) and aldosterone (ALD) levels in the study group were not significantly different from those in the control group before surgery. The levels of each index in the two groups were higher than those before and 24 h after surgery. The incidence rate of adverse reactions in the study group was lower.
Conclusion: The application of dexmedetomidine in clinical functional neurosurgery is safe and can maintain hemodynamic stability and reduce the degree of stress response, cognitive impairment, and pain caused by invasive surgery.

1. Introduction

The surgical site of neurosurgery is usually closely related to the motor and language centers of the body's nervous system, so neurosurgery is difficult and complicated. In addition, different degrees of agitation, expectoration, and pain may occur during the recovery period from anesthesia, resulting in a strong perioperative stress response [1, 2]. Restlessness and expectoration may affect surgical wound healing, lead to abnormally elevated intracranial pressure, and even lead to adverse events such as intracranial hemorrhage [3]. Therefore, it is important to implement an effective anesthesia protocol during the treatment of patients undergoing functional neurosurgery.

The anesthetic scheme in functional neurosurgery requires the following conditions to be met: stable vital signs, ability to achieve good analgesic and sedative effects, and good postoperative awakening quality as well as ability to minimize the stress response during the awakening stage, in order to prevent the occurrence of brain injury or aggravation of brain injury to the maximum extent, thereby ensuring the effectiveness and safety of the surgical treatment [4, 5]. Conventional anesthetics such as remifentanil and propofol have poor analgesic and sedative effects and have a high incidence of adverse reactions, such as the pain caused by the stimulation of the blood vessel wall when the drug is injected intravenously and the frequency of the patient's breathing after propofol injection. It slows down, decreases in magnitude, and sometimes even stops breathing. These drugs may also cause a drop in blood pressure or an abnormal heart rhythm. Dexmedetomidine, a highly selective and efficient α2-adrenergic receptor agonist, has good antianxiety, analgesic, hypnotic, and sedative effects and does not cause respiratory depression, thus effectively reducing the doses of propofol and opioids [6-8].

Although dexmedetomidine has obvious advantages compared with commonly used anesthesia drugs, its anesthesia effect in neurosurgery needs further research. In this study, we explored the application value of dexmedetomidine in neurosurgery by observing 94 patients who underwent functional neurosurgery in our hospital.

2. Materials and Methods

2.1. General Information

This study was approved by the Ethics Committee of our hospital. A total of 94 patients who underwent functional neurosurgery in our hospital from January 2019 to April 2021 were selected according to the following inclusion criteria: (1) the etiology confirmed through magnetic resonance imaging (MRI) and computerized tomography (CT) examinations, (2) American Society of Anesthesiologists (ASA) physical status grade of I to II, and (3) informed consent of patients' families. The exclusion criteria were as follows: (1) patients with organic diseases of the kidney, liver, and heart; (2) patients with circulatory system and coagulation disorders; (3) patients with cerebral infarction and intracranial hemorrhage; (4) patients with mental system and cognitive dysfunction; and (5) patients with uncontrolled diabetes and hypertension. The patients were divided into a study group and a control group according to a simple random number table, with 47 patients in each group.

2.2. Methodology

After entering the operating room, the patient's vital signs were closely monitored. Inject 10 mL/kg/h lactated Ringer's solution into the central vein. Under the supervision of an electrocardiogram, 1 μg/kg of dexmedetomidine (Hunan Kelun Pharmaceutical Co., Ltd., approved by the State Medicine H20183150) was intravenously injected into the patients in the study group. The injection was completed within 10 minutes, and dexmedetomidine was continuously infused intravenously at a rate of 0.4 μg/kg/h. At the same time, patients in the control group were intravenously injected with the same volume of normal saline. Both groups were induced by intravenous anesthesia. First, intravenously infuse propofol (Guangdong Jiabo Pharmaceutical Co., Ltd., approved by H20163406), with an initial dose of 2.5 mg/kg, then slowly instill 20 mg every 10 s, and maintain anesthesia by suction at a dose of 12 mg/min. until the patient loses consciousness. After surgery for the intracranial aneurysm, the patient was awake, breathing spontaneously, and the endotracheal tube was removed. After the patient returns to the ward, the vital signs are closely monitored.

2.3. Observation Indicators

During the perioperative period (before surgery (T0), at the beginning of surgery (T1), 30 min after the start of surgery (T2), and immediately after surgery (T3)), the hemodynamic indicators (mean arterial pressure (MAP), heart rate (HR), and peripheral capillary oxygen saturation (SpO2)) were measured in the two groups. The cognitive function of the two groups was measured preoperatively and 3 d postoperatively. According to the Mini-Mental State Examination (MMSE), the score ranges from 0 to 30 points, and the higher the score, the better the cognitive function. The pain severity at 2, 4, 8, 12, and 24 h after surgery was measured in the two groups. According to the visual analog scale (VAS) evaluation, the score ranges from 0 to 10 points, and the higher the score, the stronger the pain. The serum levels of the stress response indicators, cortisol (COR) and aldosterone (ALD), before and 24 h after operation were measured in the two groups, and the blood samples were collected and subjected to ELISA. The incidence of adverse reactions in the two groups was analyzed statistically.

2.4. Statistical Methods

The data were analyzed using SPSS 22.0 for various statistical methods, including quantitative data () analysis, t-test, enumeration data n (%), and χ2 test, and P < 0.05 indicated that the difference was statistically significant.

3. Results

3.1. General Information

There were 29 male and 18 female patients in the study group. Their ages ranged from 41 to 76 years, with an average of 58.59 ± 13.97 years. For the ASA classification, 31 cases were grade I, and 16 cases were grade II. The body mass index (BMI) was 18.5–26.8 kg/m2, with an average value of 22.67 ± 3.04 kg/m2. There were 32 male and 15 female patients in the control group. Their ages ranged from 38 to 79 years, with an average age of 60.04 ± 14.29 years. For the ASA classification, 28 cases were grade I, and 19 cases were grade II. The BMI was 17.9–27.7 kg/m2, with an average of 23.0 ± 3.0 kg/m2. Clinical data such as sex, age, ASA classification, and BMI were balanced and comparable between the two groups (P > 0.05).

3.2. Hemodynamics

Before surgery (T0), there were no significant differences in the MAP, HR, and SpO2 between the study group and the control group (P > 0.05). The MAP (89.08 ± 6.95 mmHg, 93.15 ± 6.77 mmHg, and 94.24 ± 6.58 mmHg), HR (80.18 ± 5.57 times/min, 82.92 ± 7.81 times/min, and 84.62 ± 6.40 times/min), and SpO2 (95.30% ± 8.32%, 97.72% ± 6.34%, and 96.34% ± 7.04%) at the beginning of the operation (T1), 30 min after the operation (T2), and immediately after the operation (T3), respectively, were higher than those in the control group (MAP: 82.64 ± 5.61 mmHg, 85.93 ± 5.56 mmHg, and 87.99 ± 5.2 mmHg; HR: 75.01 ± 5.14 times/min, 74.94 ± 7.03 times/min, and 78.83 ± 5.79 times/min; and SpO2: 87.79% ± 7.44%, 91.98% ± 6.11%, and 91.96% ± 6.46%) (P < 0.05, Table 1); these results indicated that dexmedetomidine could increase MAP, HR, and SpO2 levels after operation.

Table 1

Comparison of the hemodynamic indices between the two groups ().

Index	Group	Number of cases	T0	T1	T2	T3
MAP (mmHg)	Study group	47	91.34 ± 7.98	89.08 ± 6.95	93.15 ± 6.77	94.24 ± 6.58
	Control group	47	92.93 ± 8.21	82.64 ± 5.61	85.93 ± 5.56	87.99 ± 5.25
	T value		0.952	4.943	5.650	5.090
	P value		0.344	0.001	0.001	0.001
HR (time/min)	Study group	47	82.94 ± 6.95	80.18 ± 5.57	82.92 ± 7.81	84.62 ± 6.40
	Control group	47	84.11 ± 7.37	75.01 ± 5.14	74.94 ± 7.03	78.83 ± 5.79
	T value		0.792	4.676	5.206	4.599
	P value		0.431	0.001	0.001	0.001
SpO2 (%)	Study group	47	96.94 ± 9.35	95.30 ± 8.32	97.72 ± 6.34	96.34 ± 7.04
	Control group	47	98.07 ± 9.66	87.79 ± 7.44	91.98 ± 6.11	91.96 ± 6.46
	T value		0.576	4.613	4.469	3.143
	P value		0.566	0.001	0.001	0.002

3.3. MMSE Score

The preoperative MMSE score of the study group was 29.02 ± 0.79, which did not have a significant difference from that of the control group (28.97 ± 0.86) (P > 0.05). Three days later, the postoperative MMSE score of the study group was 28.91 ± 0.64, which was higher than that of the control group (27.79 ± 0.59) (P < 0.05, Table 2). Dexmedetomidine could increase the MMSE level.

Table 2

Comparison of the Mini-Mental State Examination (MMSE) scores between the two groups ().

Group	Numbers of cases	Preoperative	Postoperative 3 d	T value	P value
Research group	47	29.02 ± 0.79	28.91 ± 0.64	0.742	0.460
Control group	47	28.97 ± 0.86	27.79 ± 0.59	7.757	0.001
T value		1.350	8.821
P value		0.180	0.001

3.4. VAS Score

The VAS scores in the study group at 2, 4, 8, 12, and 24 h after surgery (2.69 ± 0.64, 2.13 ± 0.59, 1.89 ± 0.56, 1.50 ± 0.46, and 1.10 ± 0.41) were significantly lower than those in the control group (3.51 ± 0.79, 2.79 ± 0.69, 2.38 ± 0.60, 1.99 ± 0.53, and 1.59 ± 0.57) (P < 0.05, Table 3). The VAS score was decreased in patients treated with dexmedetomidine.

Table 3

Comparison of the visual analog scale (VAS) scores between the two groups ().

Group	Numbers of cases	Postoperative 2 h	Postoperative 4 h	Postoperative 8 h	Postoperative 12 h	Postoperative 24 h
Study group	47	2.69 ± 0.64	2.13 ± 0.59	1.89 ± 0.56	1.50 ± 0.46	1.10 ± 0.41
Control group	47	3.51 ± 0.79	2.79 ± 0.69	2.38 ± 0.60	1.99 ± 0.53	1.59 ± 0.57
T value		5.529	4.984	4.093	4.787	4.784
P value		0.001	0.001	0.001	0.001	0.001

3.5. Stress Response

The serum COR (208.64 ± 29.19 ng/mL) and ALD (95.64 ± 23.77 pg/mL) levels in the study group and the control group (COR, 212.04 ± 33.78 ng/mL; ALD, 92.91 ± 29.02 pg/mL) showed no significant difference before surgery (P > 0.05). The levels of each index in the two groups were higher than those before and 24 h after surgery. However, the levels of serum COR (260.26 ± 23.64 ng/mL) and ALD (141.21 ± 23.55 pg/mL) in the study group were lower than those in the control group (COR, 319.29 ± 29.11 ng/mL; ALD, 178.86 ± 26.24 pg/mL) (P < 0.05, Table 4). Dexmedetomidine also has an effect on serum COR and ALD levels.

Table 4

Comparison of the stress response indicators among the four groups (x + s).

Group	Numbers of cases	COR (ng/mL)		ALD (pg/mL)
		Preoperative	Postoperative 24 h	Preoperative	Postoperative 24 h
Study group	47	208.64 ± 29.19	260.26 ± 23.64	95.64 ± 23.77	141.21 ± 23.55
Control group	47	212.04 ± 33.78	319.29 ± 29.11	92.91 ± 29.02	178.86 ± 26.24
T value		0.522	10.792	0.499	7.321
P value		0.603	0.001	0.619	0.001

3.6. Incidence of Adverse Reactions

The incidence rate of adverse reactions in the study group was 6.38% lower than that in the control group (21.28%) (P < 0.05, Table 5), indicating that dexmedetomidine had a lower incidence of side effects.

Table 5

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

Group	Numbers of cases	Move restlessly	Choke cough	Nausea and vomiting	Respiratory depression	Total incidence
Study group	47	1 (2.13)	1 (2.13)	1 (2.13)	0 (0.00)	3 (6.38)
Control group	47	4 (8.51)	2 (4.26)	3 (6.38)	1 (2.13)	10 (21.28)
χ 2 value						4.374
P value						0.036

4. Discussion

Functional neurosurgery usually has a large wound requiring general anesthesia, and patients generally experience different degrees of restlessness, expectoration, and pain during awakening, which triggers a strong stress response. In severe cases, serious adverse events such as increased intracranial pressure may occur [9, 10]. Therefore, the anesthesia protocol that should be adopted for patients undergoing functional neurosurgery to reduce the occurrence of adverse events such as stress response and agitation has increasingly become the focus of studies, and it is of great significance to promote postoperative rehabilitation.

Propofol is a commonly used anesthetic drug in clinical practice. It has the advantages of low cost and simple application, but it can cause respiratory depression and has a high risk of agitation, which limit its clinical application [11]. Dexmedetomidine, as a new α2-adrenergic receptor agonist, can inhibit the generation of substance P and inhibit the transmission of pain signals to the cerebral cortex, possessing the advantages of significant and rapid effect, high safety, and simple operation. When used for patients undergoing functional neurosurgery, it can promote sleep, exert sedation and antianxiety effects, and inhibit the excitation of adrenergic neurons [12, 13]. A previous study [14] demonstrated that the application of dexmedetomidine during general anesthesia in patients undergoing craniotomy can effectively reduce pain and maintain hemodynamic stability, which is of great significance in ensuring the effectiveness and safety of surgical treatment. Gao et al. [15] showed that, compared with sufentanil, dexmedetomidine was more effective in maintaining hemodynamic stability, and safety was guaranteed during percutaneous tracheostomy in patients with cerebral trauma.

The results of this study showed that the levels of hemodynamic indices (MAP, HR, and SpO2) in the study group were higher than those in the control group, which was consistent with the viewpoint of the scholars described above. Moreover, the VAS scores in the study group were lower than those in the control group at various time points after surgery, the increased amplitudes of COR and ALD levels were lower than those in the control group, and the incidence of adverse reactions was lower than that in the control group. These results confirmed that dexmedetomidine had a high application value in patients undergoing functional neurosurgery, and it could maintain hemodynamic stability, reducing the degree of stress reaction caused by the invasive operation, the pain degree after the operation, and the risk of adverse reactions, consequently ensuring the effectiveness and safety of the surgical treatment.

The analysis mainly lies in the fact that dexmedetomidine is a dextral isomer of medetomidine and is an α2-adrenergic receptor agonist, with high specificity and high selectivity, which has a wide application in surgery. The sedative effect of dexmedetomidine is similar to that of the natural sleep state of the body. Even if a patient enters a deep anesthesia state, the stimulation can be awakened by slight stimulation, but it disappears, so the patient can recover from the sedation state and can shorten the awakening time. Dexmedetomidine acts on the cerebral cortex and spinal cord, and the mechanism lies in its ability to increase potassium conductivity through G-protein coupling and cell membrane hyperpolarization and by exerting excitatory effects on the spinal dorsal horn and brainstem locus coeruleus in the area where α receptors of the central nervous system are dense, thus promoting intervention subjects to enter natural non-eye-movement sleep. The short acting time and rapid effect of dexmedetomidine effectively reduce the sympathetic nerve pressure index of the body, reduce norepinephrine production, inhibit blood pressure increase that is caused by invasive operations during the operation, maintain hemodynamic stability and balance of cerebral oxygen supply and demand, and achieve good sedative effects [16, 17]. At the same time, dexmedetomidine can reduce the dosage need of other general anesthesia drugs to reduce the risk of general anesthesia-related adverse reactions [18].

In addition, the cognitive status after anesthesia is an important indicator for the clinical assessment of anesthesia safety. In this study, we found that the MMSE score of the postoperative research group was higher than that of the control group, indicating that dexmedetomidine has a significant advantage in reducing the cognitive impairment caused by surgery and general anesthesia. This may be because dexmedetomidine has little effect on the tension of the brain and can increase cerebral blood flow, avoiding edema of the brain tissue, improving brain oxygenation, protecting the brain tissue and brain cells, and ensuring the early recovery of consciousness and cognitive function. At the same time, dexmedetomidine can activate the α2-adrenergic receptor signaling pathway and affect the expression of heat shock proteins, toll-like receptors, and a variety of other proteins, thereby reducing the degree of traumatic stress response and facilitating cognitive recovery. Moreover, dexmedetomidine can reduce the secretion of norepinephrine to exert neuroprotective effects [19-21]. However, there are several limitations in the current study. Our results indicated that patients who were treated with dexmedetomidine showed a higher MAP level and heart rate during and after surgery compared with the control group; this phenomenon may be related to the kinds of surgeries we perform. In addition, the number of samples in this experiment is relatively small, and a larger number of samples and a wider range of surgeries are needed in the future to further verify the clinical value of dexmedetomidine.

5. Conclusion

In summary, findings from this study indicate that dexmedetomidine can be used safely in clinical functional neurosurgery to maintain hemodynamic stability and reduce the degree of stress response, cognitive impairment, and pain caused by invasive surgery.