El Ahmadieh, Tarek Y.; El Tecle, Najib E.; Lall, Rishi R.; Park, Anne E.; Bendok, Bernard R.
Spontaneous or nontraumatic intracerebral hemorrhage (ICH) is an important cause of mortality and morbidity worldwide.1 Management of patients presenting with spontaneous ICH includes medical therapy and, if indicated, surgical intervention.1,2 Acute reduction of elevated blood pressure is an important component of the initial medical management of such patients. This can be justified by the fact that elevated blood pressure in the setting of ICH may lead to hematoma expansion and is therefore associated with poor clinical outcome.3-5 A question that remains unanswered, however, is whether an early and rapid reduction in systolic blood pressure (SBP) could worsen outcome by causing ischemia in perihematoma brain tissue.6,7 To study this important issue, Butcher et al conducted a prospective randomized clinical trial in which 75 patients presenting with spontaneous ICH were randomized into two different target treatment groups.8,9 The study focused on evaluating the perihematoma relative cerebral blood flow (CBF) and the clinical outcome associated with each target treatment. The results were published in the March 2013 issue of Stroke.8
Between January 2007 and December 2011, 75 out of 456 screened patients were fully enrolled in the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT). The study cohort consisted of patients 18 years of age and above who presented with spontaneous ICH, evidenced on non-contrast computed tomography (CT) scan, less than 24 hours after onset. To be eligible, patients also had to present with a SBP of 150 mm Hg or more confirmed by at least 2 separate blood pressure readings that are at least 5 minutes apart. Enrolled patients were randomized into one of two target SBP groups: (1) less than 150 mm Hg, or (2) less than 180 mm Hg to be achieved within 1 hour of randomization. A non-contrast CT scan was obtained for all patients 2 hours and 24 ± 3 hours after randomization. CT perfusion images were then obtained, with special focus on the slice of greatest hematoma diameter. These images were independently studied by two readers who were blinded to the target treatment and the clinical outcome of patients. The perimeter of the intracerebral hematoma was defined on non-contrast CT scan using an intensity threshold technique. Subsequently, the area of interest was aligned 1 cm away from the hematoma not including subarachnoid, intraventricular, and blood vessel spaces (Figure 1). The mean CBF of the entire perihematoma area was used to study flow changes. Clinical assessment was performed by trained personnel who were blinded to the target treatment. The National Institutes of Health Stroke Scale (NIHSS) was performed immediately after the CT perfusion scan and at approximately 2 hours, 24 hours, 30 days, and 90 days after randomization. The Barthel index (BI) and the modified Rankin scale (mRS) were also performed at 24 hours, 30 days, and 90 days after randomization.
A total of 381 patients were excluded from the trial mainly because of evidence of secondary ICH (48%), inability to randomize patients within 24 hours (23%) and/or patients presenting with a SBP of less than 150 mm Hg (10%). Other exclusion criteria involved surgical evacuation of intracerebral hematoma, subarachnoid or intraventricular hemorrhage, contraindications to CT perfusion imaging, and ischemic stroke within 30 days prior to bleeding. Of the 75 patients enrolled in the trial, 39 patients were randomized to a target SBP of less than 150 mm Hg, whereas 36 patients were randomized to a target SBP of less than 180 mm Hg. No significant differences in terms of baseline characteristics were noted among patients in both target treatment groups. The mean SBP was 140 ± 19 mm Hg in the < 150 mm Hg target group and 162 ± 12 mm Hg in the < 180 mm Hg target group at the time when CT perfusion was performed. Of note, target blood pressure values were achieved in all patients (100%) randomized to the < 180 mm Hg group, whereas in only 79% of patients randomized to the < 150 mm Hg group (P = .005).
Upon undergoing CT perfusion imaging, patients in both target groups showed a significant decrease in the mean absolute CBF within the perihematoma area (38.7 ± 11.9 mL/100 g per minute vs 44.1 ± 11.1 mL/100 g per minute in the contralateral homologous region; P < .001) (Figure 1). Similarly, the mean absolute cerebral blood volume (CBV) was significantly lower in the perihematoma area compared to the corresponding contralateral region (P = .001). In terms of primary outcome measures, the study showed no significant difference in perihematoma relative CBF and CBV values among the two target groups (Table 1). Further, no significant difference in perihematoma relative CBF was noted when patients treated within 6 hours of presentation (0.86 ± 0.11) were compared to patients treated between 6 and 24 hours after presentation (0.89 ± 0.10) (P = .20). This was true for relative CBF values of patients in both target groups. Perihematoma relative CBF was also not significantly different among target groups in patients with larger ICH volumes (> 30 mL) (P = .82). On the other hand, relative CBF of the ipsilateral cerebral hemisphere was shown to be significantly lower in the < 150 mm Hg target group (0.95 ± 0.05) compared to that in the < 180 mm Hg group (0.99 ± 0.05) (P = .001) (Table 1). Conversely, relative CBV of the ipsilateral cerebral hemisphere was not significantly different among target groups (P = .59). The ICH volume change after 2 hours of randomization was not significantly different among target groups (P = .53) (Table 1).
In their analysis of clinical outcome, Butcher et al reported no significant difference in mortality and morbidity rates among target groups. The 30-day mortality was noted to be 17.9% in the < 150 mm Hg target group compared to 11.1% in the < 180 mm Hg group (P = .40) (Table 1). The morbidity rate as noted by the NIHSS score, 2 hours and 24 hours after randomization, was not significantly different among target groups (Table 1). Similar results were noted on the 90-day BI scores (P = .51) and 90-day mRS scores (P = .65). Of note, the median mRS scores in the < 150 mm Hg and < 180 mm Hg target groups were 2.5 and 4, respectively (Table 1).
This clinical trial showed that early reduction of blood pressure in patients presenting with spontaneous ICH does not significantly affect perihematoma CBF. Moreover, despite its notable effect on relative CBF in ipsilateral cerebral hemispheres, blood pressure reduction in the management of spontaneous ICH was shown not to significantly impact mortality and morbidity. This observation lends further support to the 2010 guidelines for the management of spontaneous ICH which stated that “in patients presenting with a systolic blood pressure of 150 to 220 mm Hg, acute lowering of systolic blood pressure to 140 mm Hg is probably safe”.1
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