non - traumatic subarachnoid hemorrhage ( sah ) occupies approximately 5 - 6% of all strokes.23 ) the incidence of sah is around six cases per 100,000 patient years , and the most common cause of sah is a rupture of a saccular cerebral aneurysm.21 ) aneurysmal rebleeding is a serious and disastrous complication of sah , and it comes with high mortality and morbidity . the incidence of aneurysmal rebleeding is considerably high within hours after the initial sah ( 21.5% within 72 hours).8 ) unfortunately , re - bleeding can not be absolutely controlled even in authoritative neurosurgical centers that performs early aneurysm repair , such as aneurysm neck clipping or endovascular coiling . several investigators have reported that rebleeding occurs more often in patients with advanced age , larger aneurysms , poor clinical condition , and increased systolic arterial blood pressure ( sbp ) on admission.5)12 ) the incidence of rebleeding was significantly higher in patients with extremely high sbp group ( > 200 mmhg ) ( 55.6% ) than in the lower sbp groups ( < 150 mmhg , 150 - 200 mmhg).7 ) therefore , it is important to control the blood pressure . nicardipine(perdipine ) is a dihydropyridine type calcium channel blocker and has strong anti - hypertensive activity and a particular cerebrovascular profile.2 ) nicardipine has been used to control blood pressure in severe hypertension after ischemic stroke , traumatic brain injury , intracerebral hemorrhage ( ich ) , and to improve vasospasm after sah.9 - 11)16)18 ) in a recent study , qureshi et al.19 ) reported the feasibility and safety of nicardipine use in treatment of acute hypertension with ich , and varelas et al.22 ) demonstrated nicardipine infusion for controlling elevated blood pressure after sah . the purpose of this study is to evaluate the effectiveness and safety of nicardipine infusion for controlling blood pressure in patients with sah , and compare the effectiveness for each fisher grade , for different dose of continuous nicardipine infusion , and for various ranges of systolic blood pressure . we prospectively evaluated 112 patients with ruptured aneurysmal sah admitted to the intensive care unit and treated them with nicardipine for 29 months period ( january 2009-may 2011 ) . the diagnosis of ruptured aneurysmal sah was made by history , clinical features , either computed tomographic angiography of the brain or four - vessels cerebral angiography to evaluate the presence of an intracranial aneurysm . the content and method was confirmed by association of clinical trial and informed consent was received from patients and/or their family members . patients with active intracranial bleeding , coagulopathy , pregnancy , myocardial infarction , chronic heart failure , and chronic kidney disease were eliminated from the study along with patients who were infused with other types of calcium channel blocker within two - hour period . fifty two patients enrolled , and their age ranged from 22 to 89 with the mean of 56.9 . nicardipine was diluted with normal saline or 5% dextrose water for intravenous injection , and it was infused until the target blood pressure was reached and settled . the goal of the treatment was to reduce and maintain the sbp less than 140 mmhg and diastolic blood pressure ( dbp ) less than 100 mmhg ( mean arterial pressure less than about 110 mmhg ) within 24 hours from the treatment started . continuous injection period is when blood pressure control failed even after the bolus injection of nicardipine . the continuous intravenous nicardipine injection was initiated with a rate of 5 mg / hr . if the mean arterial pressure was not reduced to 110 mmhg after 15 minutes , the infusion dose was increased by 2.5 mg / hr . the 2.5 mg / hr increments continued every 15 minutes until the maximum dose of 15 mg / hr was reached . we also evaluated the influence of infusion dosage of nicardipine according to sbp / dbp . 1 mg of nicardipine was used in patients with sbp between 140 and 160 mmhg , and 2 mg in patients with sbp between 161 and 180 mmhg . fifty two patients , who fulfilled the condition , were injected with nicardipine . their demographics and clinical characteristics are presented in table ( table 1 ) . in forty patients who were not responsive to bolus injection , the mean blood pressure in three periods were compared . from pre - injection period ( 145.6/80.3 mmhg ) , 11.4/9.0 mmhg was reduced after bolus injection , whereas 24.7/17.3 mmhg was reduced after continuous injection . the effect of nicardipine in controlling blood pressure was statistically significant ( p < 0.001 ) ( table 2 ) . effectiveness of nicardipine was analysed according to three conditions : fisher grade , continuous infusion dose of nicardipine , and ranges of systemic blood pressure . at first , all the subgroups of fisher grade showed decrease in sbp / dbp using nicardipine . the mean sbp / dbp decreased by 38.0/22.5 mmhg ( p = 0.037/p = 0.038 ) in fisher grade i ( n = 4 ) , 15.9/7.7 mmhg ( p = 0.001/p = 0.035 ) in grade ii ( n = 10 ) , 22.2/15.6mmhg ( p < 0.001/p = 0.004 ) in grade iii ( n = 16 ) , and 28.6/17.2 mmhg ( p < 0.001/p = 0.001 ) in grade iv ( n = 18 ) , and all of them were statistically significant . ( sbp between subgroups p = 0.144 , dbp between subgroups p = 0.299 ) ( table 3 ) . secondly , each subgroups with different dosage of nicardipine lowered sbp / dbp . in low dose group ( n = 20 ) ( 5 mg / hr ) , the mean sbp / dbp decreased by 11.8/7.9 mmhg ( p < 0.001/p = 0.002 ) . it decreased by 13.1/9.7 mmhg ( p < 0.001/p= 0.046 ) in medium dose group ( n = 12 ) ( 6 - 10 mg / hr ) , and 15.0/9.2 mmhg ( p = 0.003/p = 0.007 ) in high dose group ( n = 10 ) ( 11 - 15 mg / hr ) ( sbp between subgroups p = 0.575 , dbp between subgroups p = 0.404 ) ( table 4 ) . finally , 1 mg of nicardipine was used in patients with sbp between 140 and 160 mmhg ( n = 18 ) , and 2 mg in patients with sbp between 161 and 180 mmhg . in patients with sbp below 160 mmhg ( n = 9 ) , the mean sbp / dbp decreased by 19.8/14.2 mmhg ( p < 0.001/p < 0.001 ) , and it dropped by 48.0/30.8 mmhg ( p < 0.001/p = 0.008 ) in patients with sbp above 160 mmhg . there was significant decrease in blood pressure in both groups ( sbp in both groups p < 0.001 , dbp in both groups p = 0.01 ) ( table 5 ) . in one case , which infused 2.5 mg / hr of nicardipine , the sbp of the patient dropped to 94 mmhg and dbp to 33 mmhg ; thus , nicardipine had to be pre - terminated . tachycardia with heart rates more than 120 beats per minute appeared in two patients , and arrhythmia was combined in two patients , in which one of them showed ventricular premature contraction , and another showed atrial fibrillation . nicardipine , a dihydropyridine calcium channel antagonist , is a vasoselective agent with minimal cardiac inotropic effects.23 ) this is the ideal agent for short - term management of hypertension because of short half life and relatively rapid onset / offset of action in lowering blood pressure with minimal adverse events.6 ) hypotension , arrhythmia and tachycardia were some adverse effects observed in this study but there was no severe events . there has been studies comparing the effectiveness of nicardipine and sodium nitroprusside or nicardipine and labetalol and evaluating effectiveness of nicardipine in traumatic brain injury , sah , ich , arteriovenous malformation , and hypoxic brain injury.13)16)20 ) recently , varelas et al.22 ) reported effectiveness and safety of nicardipine infusion in reducing sbp and dbp to pre - specified goal . intravenous nicardipine has already been included in the published guidelines for blood pressure control in ischemic stroke , ich.1)4 ) the recently published guidelines for sah also include nicardipine , however , without available data for such a use.3 ) in this study , continuous injection was the most effective method in decreasing blood pressure compared with bolus injection . in some cases , which we manipulated the injection method from bolus to continuous , the influence of bolus injection can not be ignored even though nicardipine is a short acting agent . this study also showed no significant difference in effectiveness of nicardipine to control blood pressure for each fisher grade and for different continuous dosage of nicardipine . nicardipine showed significant decrease in all the subgroups of each categories ; however , there was no significant difference within subgroups of fisher grade and dosage . on the contrary , the effectiveness of nicardipine was significantly different between a group of sbp with 140 - 160 mmhg and 161 - 180 mmhg . transient complications , such as hypotension , arrhythmia , and tachycardia , appeared , but patients recovered without any permanent deficit . the risk of rebleeding decrease as the blood pressure decreases , but lowering the blood pressure is not everything . one study reported a increase in rebleeding risk with blood pressure over 160 mmhg compared with 140 mmhg , and rebleeding incidence decreased when anti - hypertensive treatment was used.17 ) in contrast , risk of cerebral infarction rate increases with low blood pressure.24 ) the optimal blood pressure after sah would dependent on multiple factors . in addition , appropriate management of blood pressure is necessary because most rebleeding occurs due to the change of blood pressure rather than absolute blood pressure level itself.15 ) the most recent guideline for the management of sah recommends that " blood pressure should be monitored and controlled to balance the risk of stroke , hypertension - related rebleeding , and maintenance of cerebral perfusion pressure " as class i , level of evidence b.3 ) until systematic treatment algorithms are developed , the optimal blood pressure may vary considerably and be dependent on physician 's preferences . the limitation of this study is that there is no correlation between age , clinical or past medical history and the influence that these factors will have on patient 's blood pressure . also medical conditions such as seizure or hydrocephalus were not considered , and the number of study population was too small to represent the accurate outcome . the initial blood pressure of each patient and the reaction to injection were not reflected on setting and reaching a goal blood pressure . nicardipine is an effective medication in controlling acute hypertension or dropping blood pressure in sah . because continuous infusion of nicardipine has better effects in blood pressure control , it is recommendable when blood pressure is not controlled with bolus infusion if there is no symptom of adverse effects . there was no significant difference in effectiveness of nicardipine within subgroups of fisher grade and infusion dosage . it was found that higher dose of nicardipine injection with higher sbp is more effective in controlling blood pressure . a systemic study with larger number of patients will be necessary to plan a more precise guideline for the use of nicardipine in controlling blood pressure with sah .
objectivethe purpose of the study is to determine the effectiveness and safety of nicardipine infusion for controlling blood pressure in patients with subarachnoid hemorrhage ( sah).methodswe prospectively evaluated 52 patients with sah and treated with nicardipine infusion for blood pressure control in a 29 months period . 
 the mean blood pressure of pre - injection , bolus injection and continuous injection period were compared . 
 this study evaluated the effectiveness of nicardipine for each fisher grade , for different dose of continuous nicardipine infusion , and for the subgroups of systolic blood pressure.resultsthe blood pressure measurement showed that the mean systolic blood pressure / diastolic blood pressure ( sbp / dbp ) in continuous injection period ( 120.9/63.0 mmhg ) was significantly lower than pre - injection period ( 145.6/80.3 mmhg ) and bolus injection period ( 134.2/71.3 mmhg ) , and these were statistically significant ( p < 0.001 ) . in each subgroups of fisher grade and different dose , 
 sbp / dbp also decreased after the use of nicardipine . 
 these were statistically significant ( p < 0.05 ) , but there was no significant difference in effectiveness between subgroups ( p > 0.05 ) . 
 furthermore , controlling blood pressure was more effective when injecting higher dose of nicardipine in higher sbp group rather than injecting lower dose in lower sbp group , and it also was statistically significant ( p < 0.05 ) . during the infusion , hypotension and cardiogenic problems were transiently combined in five cases . 
 however , patients recovered without any complications.conclusionnicardipine is an effective and safe agent for controlling acutely elevated blood pressure after sah 
 . a more systemic study with larger patients population will provide significant results and will bring solid evidence on effectiveness of nicardipine in sah .