Progress in Analgesic-Sedative Treatment in Perioperative Period of Hypertensive Intracerebral Hemorrhage

Hypertensive intracerebral hemorrhage (HICH) refers to intra cerebral hemorrhage at basal ganglia, thalamus, ventricle, cerebellum and brainstem in patients with history of explicit hypertension disease, excluding secondary cerebral hemorrhage caused by trauma, vascular structural disorders, coagu-lation disorders, hematologic diseases, systematic diseases and neoplastic diseases. HICH is characteristic of high morbidity, fatality rate, disability rate and recurrence rate. HICH is the most common type of spontaneous cerebral hemorrhage and various surgical interventions are one of the major treatments for HICH. Surgical treatment is to eliminate hematoma, relieve oppression of hematoma on surrounding brain tissues, lower intracranial pressure and alleviate secondary brain tissue damages, thus enabling to decrease fatality rate of patients and improve the long-term quality of life. Patients with HICH often may have different degrees of coma, pains, dysphoria, anxiety and delirium in the postoperative period. After central pivot was damaged, the sympathetic central excitability spreading is strengthened in the state of cortical inhibition, which also might be accompanied by paroxysmal sympathetic hyperexcitation syndrome to strengthen disease conditions of patients and thereby influence subsequent treatment. Several professional guidelines all recommend analges-ic-sedative treatment as an important component of ICU therapy. However, it lacks support by large sample sized clinical research results of analgesic-sedative treatment of HICH in the postoperative period. This study analyzed literature concerning analgesic-sedative treatment of HICH in the postoperative period in recent years, aiming to guide specific clinical implementation.


Pathogenesis of Hypertensive Intracerebral Hemorrhage
Hypertension can cause pathological changes of general organs and blood vessels. Cerebral vessels develop retrogression and arteriosclerosis under long-term high pressure to adapt to hypertension. The wall of cerebral arterioles is thickened to resist high pressure and prevent the increase of the subsequent cerebral microcirculation perfusion pressure. All of these changes are particularly serious in arteriae perforantes at basal cerebral. Therefore, intracerebral hemorrhage is the collaborative result of anatomical features of cerebral vessels, pathological changes of blood vessel walls and a sudden increase of blood pressure [1].
Anatomical features of cerebral vessels: the wall of cerebral arterioles is relatively thin and there are a few medium membrane muscle fibers, without elastic fiber layer. The adventitia is significantly weaker than arteries of other organs.
Moreover, basal cerebral perforating branches, such as lenticulostriate arteries and thalamic perforating branch are all originated from the terminal branch of the main blood vessels and most of them form an angular of 90˚ with the main blood vessels. Due to these anatomical features, intraluminal pressure is significantly higher than pressure of intracerebral blood vessels with the same diameter at other positions. Hence blood vessels become the predilection site of hypertensive intracerebral hemorrhage (HICH).
Pathological changes of blood vessel wall: the wall of cerebral arterioles develops hyaline change or fibroid degeneration and even local tiny hemorrhage, ischemia or necrosis due to hypertension. The inner elastic fiber layer is damaged to form small sacculated aneurysm or dissecting aneurysm. Such dissecting aneurysm is often seen in patients over 50 years old and it mainly distributes in basal ganglion, pons, white matter and cerebral perforator arteries. When the blood pressure increases suddenly, the microaneurysm breaks to cause cerebral hemorrhage.
Hypertension is the primary cause of pathological changes of arterial wall.
When blood pressure increases suddenly, the weak points of the arterial wall are easy to develop rupture hemorrhage. Blood pressure transmits in the pulse way and thrombus is formed at rupture of arterial wall after hemorrhage. The arterial wall also becomes narrow due to oppression by hematoma and blood flow resistance increases, thus stopping hemorrhage automatically.
By analyzing pathogenesis of HICH, we found that blood pressure is the sole regulating factor in the postoperative period. The goal of controlling secondary hemorrhage in patients with HICH can be realized by controlling blood pressure in the postoperative period.

Significance of Analgesic-Sedative Treatment in Patients with HICH during Postoperative Period
It is reported by studies that postoperative sedative treatment is an independent factor that influence prognosis of craniotomy evacuation of hematoma in patients with HICH [2]. It can stabilize postoperative blood pressure effectively,  There's still controversy over daily interrupted sedation to patients with HICH.

Postoperative Analgesic-Sedative Strategy and Mode to Patients with HICH
The dramatic changes of consciousness might induce increases in blood pressure and intracranial pressure, thus causing psychological stress [8] and even secondary hemorrhage. In particular, the benefits of daily interrupted sedation must be balanced with the risk of further cerebral hemodynamic deterioration upon sudden withdrawal of analgesic-sedative treatment in the acute phase. Patients who have risks of intracranial hypertension, receiving target body temperature management or continuous state of intractable epilepsy shall avoid daily interrupted sedation. It is suggested to withdrawing the sedation state gradually rather than suddenly. Early target-oriented sedation [9] was proposed by Sheha-

Characteristics of Common Analgesic-Sedative Drugs to Patients with HICH
For patients with HICH, two basic principles shall be observed in selecting analgesic-sedative drugs. On one hand, drugs have no additional damages to brain tissues and they won't cause risks of increased intracranial pressure and de- Remifentanil: it is a fentanyl μ-type opioid receptor agonist and it mainly binds with α-1-acidoglycoprotein. It can be hydrolyzed quickly in tissues and blood, and acts in 1 -3 min. However, the acting time of remifentanil is short and the half-life period is only 3 -10 min, without causing liver and kidney injuries. Recent studies found that remifentanil can shorten duration of mechanical ventilation and length of stay in ICU significantly [10]- [15].
Sufentanil: it has very strong analgesic effect, which is 5 -10 times that of fen- Midazolam is a benzodiazepine and can provide sedative-hypnotic, anti-anxiety,

Conclusion
Analgesic-sedative treatment of patients with HICH in postoperative period is of great significance to prognosis of HICH. However, it still lacks high-level evidence-based medicine to guide postoperative analgesic-sedative treatment for HICH. Now, programmed sedation and early target-oriented sedation are applied frequently. Midazolam, dexmedetomidine, sufentanil and remifentanil are relatively ideal drugs. It is suggested to combine analgesic-sedative drugs according to individual schemes to realize good therapeutic effects and mitigate side effects caused by a high dosage of a drug.

Fund-Supported Project
"Xingchen" Scientific Research Fund project.

Conflicts of Interest
The author declares no conflicts of interest regarding the publication of this paper.