Spontaneous intracerebral hemorrhage (ICH) is a hemorrhage occurring in the brain parenchyma that was caused by the non-traumatic spontaneous rupture of a cerebral artery, arteriole, vein or capillary in an adult. ICH is classified as primary or secondary ICH based on its etiology. Primary ICH accounts for 80–85% of all cases of spontaneous ICH and mainly includes hypertensive ICH (50–70%) [
1], amyloid angiopathy-associated ICH (20–30%), and ICH of unknown cause (10%). Secondary ICH includes ICH caused by a venous malformation, aneurysm, arteriovenous fistula, cavernous malformation, hematological disorder or coagulopathy, hemorrhagic cerebral infarction, venous sinus thrombosis or adverse drug reaction or Moyamoya disease [
2]. ICH accounts for 25–55% of brain stroke cases in Asian countries and 10–15% of such cases in European and American countries [
3]. Increased blood pressure (BP) has already been confirmed as a risk factor for ICH development and a poor prognosis [
4,
5]. A systematic review showed that a 10-mmHg increase in systolic BP caused a 42% increase in the risk of ICH [
5]. Approximately 90% of ICH patients experience an immediate increase in BP after disease onset [
6‐
8]. BP elevation in the acute phase of ICH is associated with a poor prognosis, is caused by mechanisms of action, such as a local increase in the initial hemorrhage or an early hematoma expansion at hemorrhagic sites [
9‐
14], and is associated with an increased risk of early recurrent hemorrhage, serious cerebral edema [
15,
16], and recurrent stroke [
17]. In an observational study of 1701 patients, patients with a mean arterial pressure of 134 mmHg on admission were more likely to have fatal outcomes, while those with a mean arterial pressure of 120 mmHg on admission were more likely to survive [
18]. The current American Heart Association guidelines suggested that inducing a rapid decrease in BP to 140 mmHg is safe in ICH patients with no obvious antihypertensive contraindications [
19‐
21]. However, the results of several large randomized controlled trials (RCTs) completed in recent years have presented significantly different findings [
22‐
25]. A meta-analysis that included 4360 subjects enrolled in five RCTs showed that intensive acute BP lowering (to a target BP of 140 mmHg) was safe but did not seem to provide an increased clinical benefit in terms of functional outcomes [
26]. These results were substantially different from those presented in previous studies, and differences in inclusion criteria (i.e., enrolled patients exhibited small ICH volumes and a small number of warfarin-associated hematomas) and complications in addition to differences in early BP control rates and variability in BP increases may represent major causes of the inconsistencies observed among these studies [
20‐
25]. Because the wide range of BP-lowering medications used among these studies have different modes of administration, it was not possible to identify an optimal antihypertensive therapy for rapid and stable BP lowering in ICH [
26].
Some studies have shown that the stress response, pain, and intracranial pressure (ICP) increases are factors that cause acute BP increases in ICH patients [
19,
27]. The primary principles underlying treatment for acute BP increases in ICH are to keep the patient quiet, restore BP to a normal level, decrease BP variability, and lower the chance of recurrent hemorrhage [
23,
28,
29]. Combining analgesia and sedation is a critical component of this strategy for which there is global consensus [
19,
30]. Remifentanil is a fentanyl μ-type opioid-receptor agonist with strong and fast-acting analgesic effects that does not induce ICP elevation [
31], and dexmedetomidine is an α
2-adrenergic agonist that inhibits sympathetic activity and reduces norepinephrine release [
31]. Remifentanil and dexmedetomidine are mainly used as anesthetic and analgesia/sedation medications in critical patients. ICH is one of the most common critical diseases, and analgesia/sedation has been shown to control pain and anxiety and to provide a neuroprotective effect in the acute phase of ICH [
31]. Therefore, our research group developed a treatment strategy in which sufficient analgesia is applied in combination with a minimal sedation program as an effective and safe early antihypertensive treatment. We hypothesize that applying sufficient analgesia in combination with a minimal sedation program will involve the use of remifentanil for pain relief and dexmedetomidine for antisympathetic activity to restore elevated BP to normal levels in patients with spontaneous ICH, and we further hypothesize that this strategy will be more effective than conventional symptomatic antihypertensive treatment for controlling BP.