A Pilot Randomized Trial of Induced Blood Pressure Elevation: Effects on Function and Focal Perfusion in Acute and Subacute Stroke

Abstract

Background: Small, unrandomized studies have indicated that pharmacologically induced blood pressure elevation may improve function in ischemic stroke, presumably by improving blood flow to ischemic, but noninfarcted tissue (which may be indicated by diffusion-perfusion mismatch on MRI). We conducted a pilot, randomized trial to evaluate effects of pharmacologically induced blood pressure elevation on function and perfusion in acute stroke. Methods: Consecutive series of patients with large diffusion-perfusion mismatch were randomly assigned to induced blood pressure elevation (‘treated’ patients, n = 9) or conventional management (‘untreated’ patients, n = 6). Results: There were no significant differences between groups at baseline. NIH Stroke Scale (NIHSS) scores were lower (better) in treated versus untreated patients at day 3 (mean 5.6 vs. 12.3; p = 0.01) and week 6–8 (mean 2.8 vs. 9.7; p < 0.04). Treated (but not untreated) patients showed significant improvement from day 1 to day 3 in NIHSS score (from mean 10.2 to 5.6; p < 0.002), cognitive score (from mean 58.7 to 27.9% errors; p < 0.002), and volume of hypoperfused tissue (mean 132 to 58 ml; p < 0.02). High Pearson correlations between the mean arterial pressure (MAP) and accuracy on daily cognitive tests indicated that functional changes were due to changes in MAP. Conclusion: Results warrant a full-scale, double-blind clinical trial to evaluate the efficacy and risk of induced blood pressure elevation in selective patients with acute/subacute stroke.

Induced-hypertension in progressing lacunar infarction

“…Results of our study supported that phenylephrine inducedhypertension is a beneficial way to restore motor progression in patients with progressing lacunar infarction, concurring with prior studies [5,[13][14][15][16][17]21]. There has been no clear explanation on the mechanism of progressing lacunar infarction and motor recovery after induced hypertension [5,[22][23][24][25].…”

“…Hillis et al restored the BP of an aphasic patient and the symptoms improved due to reperfusion of the Wernicke's area [5]. A randomized prospective pilot study using induced-hypertension also showed that significant improvement of NIHSS, cognitive score and volume of hypoperfused tissue on perfusion-weighted imaging [15]. Various studies have pointed out the existence of perfusion defects in lacunar infarction, and a recent report revealed that mean systolic BP was lower in early deteriorating patients with abnormal PWI [7,8,26].…”

“…However, it was not the predictor when applying the Model 1 criterion. Previous studies have used various goals of BP elevation for the restoration in acute ischemic stroke, there are reports showing that patients with 20% or more BP elevation was significantly associated with good outcome in ischemic stroke patients [14][15][16]. According to Ohm's law of hemodynamics, cerebral perfusion pressure can be directly correlated with cerebral blood flow in the perforating arteries due to the lack of resistant arterioles [31].…”

“…DWI = diffusion weighted image; BG = basal ganglia; CR = corona radiata. [14,15,17]. This low adverse event rate is due to the low affinity of phenylephrine to the beta receptor of the heart and because of the lower coincidence of coronary artery disease, administration of phenylephrine can be a safer option to patients with progressing lacunar infarction [32].…”

“…However, there have been no comparative studies on the effect of induced-hypertension in patients with progressing lacunar infarction, although preliminary studies have suggested that inducedhypertension therapy could play an advantageous role in large arterial atherosclerotic infarction with ischemic penumbra having impaired cerebral autoregulation [13][14][15][16][17]. Therefore, we investigated the outcome of phenylephrine induced-hypertension and which factors were related to the clinical response of induced-hypertension therapy in patients with lacunar infarction with early motor deterioration.…”