Pharmacologically Induced Hypertension Therapy for Acute Stroke Patients

In patients who experience acute stroke, excessive blood pressure (BP) lowering may result in early neurological deterioration (END) and unfavorable clinical outcomes. Thus, pharmacologically induced hypertension (PIH) may be effective for patients with signs of END. Although a few studies have reported potential benefits, the feasibility and safety of PIH remain unclear. We aimed to identify the characteristics of patients who require PIH therapy and to examine the feasibility, safety, and potential efficacy of PIH. At the Asan Medical Center, we have been performing PIH therapy since 2011 for patients who exhibit END or are at increased risk for END, such as those with fluctuating neurological symptoms, based on the results from previous studies. Although END was defined as an increase in National Institutes of Health Stroke Scale (NIHSS) score ≥2, patients with a 1-point increase were occasionally included according to the attending neurologist’s judgment. PIH was not performed in patients with systolic BP >180 mm Hg or diastolic BP >110 mm Hg, ventricular tachycardia, or symptomatic heart or renal failure. However, because PIH is not an established treatment, some patients with END were treated by augmenting fluid therapy without PIH according to the discretion of attending physicians. For PIH, BP elevation of 15% to 25% over baseline was targeted, with a maximum systolic BP of 220 mm Hg. Phenylephrine (50 mg) mixed with 250 mL of normal saline was intravenously administered at a rate of 0.3 μg/kg/min and titrated every 30 to 60 minutes. PIH was usually maintained for 5 days and tapered thereafter. If END recurred, PIH was re-administered for several days. Two groups were selected as controls: the first was matched with age and sex (CT1) and, the second, with an additional stroke subtype (CT2). Considering the expected unfavorable outcome in patients with END, a favorable functional outcome was defined as a modified Rankin Scale (mRS) score of ≤3 at 3 months post-stroke. “Early responsiveness” was defined when patients exhibited neurological improvement (NIHSS score ≥2 improvement or physician’s documentation for neurological improvement) within 1 day after PIH initiation. BP was recorded at four time points: the first-measured hospital BP (initial BP [iBP]); BP checked immediately before starting PIH (baseline BP [BP0]); BP checked at 7:00 AM 1 day after starting PIH (BP1); and BP checked at 7:00 AM 1 day after completing PIH (end BP [eBP]). This study was approved by the Institutional Review Board of Asan Medical Center, and the requirements for informed written consent was waived. Between 2011 and 2016, 121 patients were treated with PIH (mean±standard deviation age, 65.9±12.7 years; women, 40%). Compared with CT1 patients, PIH patients more often had small vessel disease (SVD, 42.3% vs. 19.8%) and large artery disease (LAD, 41.3% vs. 31.4%), and less often experienced cardioembolic stroke (4.15% vs. 34.7%) (P<0.001, chi-square test). As stroke subtype may be associated with patient outcome, subsequent analyses was performed with CT2 patients. PIH patients had significantly higher systolic iBP, higher initial NIHSS score, and more often had END compared with CT2 patients (Table 1). In the PIH group, the mean arterial pressure of BP0 (96.9±13.4 mm Hg) decreased from that of iBP (108.5±17.9 mm Hg). After PIH treatment, mean systolic BP1 (166.4±19.3 mm Hg) was elevated by 24.8%±19.3% from BP0 (135.3±18.6 mm Hg), and diastolic BP1 (83.6±13.7 mm Hg) was elevated by 9.3%±9.2% from BP0 (77.7±12.9 mm Hg). The mean PIH duration was 5.8±2.7 days. The mean time to achievement of target BP was 7.6±4.6 hours. Nine patients developed hemorrhagic transformation—three in the PIH group and six in the CT2 group—and there were no Pharmacologically Induced Hypertension Therapy for Acute Stroke Patients