Hypertensive cerebral hemorrhage (HCH) is a serious threat to human health, causing high mortality and morbidity (1). The oppression on the surrounding brain tissue caused by hematoma can be removed through surgical resection by relieving secondary brain injury and this method, known as brain hematoma clearance, as well as decompressive craniectomy are widely used in clinical settings (2). During the perioperative period, the body's stress response can be effectively reduced by the rational use of sedative to prevent blood pressure fluctuations that cause secondary bleeding. However, traditional sedatives and analgesic drugs such as benzodiazepines or opioid are often insufficient to lead to sedative and analgesic effects (3).

The administration of a high dose of these drugs lead to excessive sedation and respiratory depression, thereby affecting circulatory and respiratory functions and becoming life threatening. Dexmedetomidine is a novel α₂ adrenoceptor agonist with high selectivity that can produce a good sedative effect. Furthermore, the sympathetic resistance effect of this drug, decreases the sympathetic excitation caused by surgery and anesthesia and thus helps the stability of haemodynamics. The drug also has certain neuroprotective effects such as, easy wake up after sedation and prevention of respiratory depression (4). Considering the above facts, we have analyzed the suitability of the administration of dexmedetomidine as a sedative and analgesic for patients with HCH during the perioperative period.

Dexmedetomidine is a novel highly selective α₂–adrenergic receptor agonist with a good sedative effect and without respiration inhibition effect (6,7). Previous findings have shown that α₂ adrenergic receptors widely exist in the central nervous system, peripheral nervous system (somatic nerves and autonomic nerves) and autonomic ganglion, especially in tissues or organs dominated by sympathetic afferent nerves, such as vascular smooth muscle (8). A previous study has found that the α₂ adrenergic receptor has three different receptor subtypes: α_2A, α_2B and α_2C receptor (9). The receptors can connect with G protein and have a total of seven transmembrane segments that can couple with G0/G1 signal system and, inhibit the activation of adenylate cyclase activity and synthesis of cAMP, as well as inhibit the calcium channel and activate the potassium channel. Their different distribution determines their different functions.

The α_2B receptors are mainly distributed in thalamus while α_2A and α_2C receptors are widely distributed in the brain. The α_2A receptors are highly distributed in the locus coeruleus area and may inhibit the activity of norepinephrine cells of these regional brain tissues. α_2A receptors exist in the anterior and posterior synapsis and could inhibit the release of norepinephrine and the activity of sympathetic nerve cells (8). Dexmedetomidine (8) may inhibit the generation of cGMP in a dose-dependent manner. Furthermore, α_2A receptors play an important role in the main pharmacological and therapeutic effects of dexmedetomidine. From experiments on mice, it was found that when α_2A receptors were blocked, the sedation, anesthesia and analgesic effects of dexmedetomidine disappeared but when α_2B and α_2C receptors were blocked, mice were able to produce normal pharmacological responses to dexmedetomidine. Previous findings showed that dexmedetomidine mediated the hypnotic reactions of animals via α_2A receptors in the locus coeruleus, as animals under long-term medication developed a certain drug resistance to the hypnotic effect of dexmedetomidine and calcium channel blockers were able to reverse the drug resistance (10).

Dexmedetomidine, after combining with presynaptic α₂ adrenergic receptors of sympathetic nerve endings, inhibited the release of noradrenaline (8). The study also revealed that, dexmedetomidine, after combining with the postsynaptic α₂ adrenergic receptors of the central nervous system were able to reduce the activity of the sympathetic nervous system, thereby lowering blood pressure and HR.

Dexmedetomidine combined with intramedullary α₂ adrenergic receptors, promoted analgesia and sedation, and inhibited anxiety (7). Results of a clinical study found that, dexmedetomidine reduced the dosage of other anesthetic drugs, reduced the sympathetic excitatory effects caused by anesthesia and/or surgery, and stabilized the dynamics of blood flow (11). The sedative, hypnotic and anxiolytic effects of dexmedetomidine were mainly attributed to its combination with the genotypes of sub-types of α₂ receptors in the locus coeruleus area. In mice, it was found that, when α_2A receptors were blocked, the sedative, anaesthetic and analgesic effects of dexmedetomidine disappeared (12). In humans, it was found that the blood flow signals caused by dexmedetomidine were similar to the signals produced from natural sleep (13). Dexmedetomidine was able to stimulate α_2C receptors to produce anti-anxiety effects, and the mice without α_2C receptors had shortened attack latency and significantly enhanced alarm reactions (14). Dexmedetomidine also stimulated α_2A receptors to produce analgesic effects (15), except the α_2A receptors located above the spinal cord.

Dexmedetomidine inhibition of tracheal intubation response may be caused by its excitation of α₂ adrenergic receptors, which reduce the release of catecholamine, thereby producing obvious central sedation and sympathetic inhibition effects, and reducing the cardiovascular stress responses at incubation. The study of Venn et al (16), in which 119 postoperative patients from intensive care unit (ICU) operation were given dexmedetomidine or a placebo, showed that the dosages of auxiliary sedative and analgesic drugs of patients in the dexmedetomidine group were significantly less than those of the control group, and dexmedetomidine patients were relatively cooperative and suffered less conscious pains. Another study on ICU patients who underwent mechanical ventilation indicated that, in order to achieve a better respiratory support effects, propofol-administered patients needed 3− fold more opioid drugs than dexmedetomidine patients. The dexmedetomidine patients were also more easily awakened and more cooperative to ventilator support, and they were able to accurately recollect the lenght of stay in ICU after leaving, while propofol patients were incapable of such recollection (17).

The present study has found that dexmedetomidine reduced the dosage of other anesthetic drugs, reduced the sympathetic excitatory effects caused by anesthesia and/or surgery, and stabilized the haemodynamics (11). In addition, the effects of dexmedetomidine on respiration were much slighter (18). During the perioperative period, most patients feel fear, are anxious or worried, which inevitably results in a series of excitatory stress responses of sympathetic nerves during anaesthesia and operation, such as increased HR and blood pressure. Dexmedetomidine inhibited the excessive excitation of sympathetic nerves through activation of α₂ adrenergic receptors of the central nervous system, thereby restraining the excessive release of catecholamine substances in sympathetic nerve terminals, improving the stability of hemodynamics in the perioperative period, effectively preventing or improving heart ischemia.

From a volunteer test, it was found that dexmedetomidine infusion (plasma drug concentration was 0.5 ng/ml and 5 ng/ml) reduced myocardial perfusion, myocardial oxygen consumption, and prevented myocardial ischemia (19). Intravenous injection of dexmedetomidine before anesthesia significantly inhibited the increase of blood pressure and the acceleration of HR caused by laryngoscopy and tracheal intubation, and also reduced the dosages of anaesthetics and opioid drugs (20). A randomized comparative study on 30 patients who received awake nasotracheal intubation showed that, compared with fentanyl patients, the dexmedetomidine patients had better tolerance and more stable hemodynamics (21,22).

In an earlier study from our laboratory (Junhui, Master's dissertation), it was found that the hemodynamics of patients at pump infusion of dexmedetomidine and tracheal intubation were relatively stable and ECG was not significantly changed (23,24). The study also showed that dexmedetomidine reduced the secretion of catecholamine before and after awake tracheal intubation, thereby effectively preventing the adverse stress reactions of the cardiovascular system during the intubation process but not significantly affecting the patients' respiration. The result of the study indicated that, application of dexmedetomidine in awake blind tracheal intubation via oral cavity led to stable hemodynamics. In a clinical setting, the adverse reactions of dexmedetomidine mainly includes sinus tachycardia, tachycardia and even cardiac arrest, hypotension, hypertension as well as other cardiovascular diseases. Other studies have reported nausea, fever, dry mouth and other adverse reactions due to dexmedetomidine (25,26).

In the present study, the two groups had no serious adverse reactions. The patients in the dexmedetomidine group had no respiratory depression, ventilation difficulties, increased blood pressure or chest wall stiffness. In comparison with the midazolam group, adverse reactions in the dexmedetomidine group were significantly reduced. Prior to surgery, the patients' specific conditions were comprehensively evaluated, especially the heart functions. For the patients with bradycardia, insufficient blood volume and cardiac conduction block, dexmedetomidine was used with caution (17). Dexmedetomidine may also be useful in protecting the nerves.

Concerning adjuvant drugs, patients of the dexmedetomidine group were given 1 µg/kg dexmedetomidine, which was diluted in normal saline to a final volume of 20 ml via pump infusion for 10 min, and followed by 0.5 µg/kg.h as a maintenance dose. Before craniotomy and at extubation, sedative effects proved satisfactory. Most patients tolerated extubation, hemodynamics was stable, SPO₂ and P_ETCO₂ were not seriously affected, fluctuation of blood pressure was not obvious, no respiratory depression occurred, and the HR of several patients were significantly reduced albeit maintained over 60 beats/min, cardiac output was not affected.

By contrast, under the sedative dose (0.05 mg/kg), although patients in the midazolam group failed to inhibit a hemodynamic response at craniotomy, some patients showed obvious agitation at extubation, SPO₂ and P_ETCO₂ were seriously affected, and several patients had respiratory depression. In the course of intracranial hematoma clearance of HCH, hypoxic-ischemic brain damage of the blood supply area led to the changes in the levels of many enzymes or proteins and both NSE and S100β were sensitive biochemical indicators of brain injury. NSE is a specific intracellular protein that exists in nerve cells and neuroendocrine cells. It monitors neuron injuries, and the changes in the level of NSE can effectively reflect the damage status of neurons. S100β exists in astrocytes, oligodendrocytes and other neurogliocytes and its levels reflect the damage status of neurogliocytes. The detection results of NSE and S100β in this study indicated that dexmedetomidine was effective for protecting the brains of HCH patients under craniotomy, but the specific protective mechanism needs to be further studied.

In conclusion, dexmedetomidine provided safe and effective sedation for HCH patients who received craniotomy. It also effectively reduced blood pressure and HR, reduced the dosage of anesthesia, alleviated the cardiovascular responses in anesthesia recovery period, prevented respiratory depression, and protected the brain. It is an ideal sedation adjuvant drug, and is worthy of wide application in neurosurgery.