a-1, ß-1, ß-2 receptor antagonist

5-10 min

2-12 hr

10-80 mg IV q 10 min up to 300 mg/d IV infusion: 0.5-2 mg/min

Congestive heart failure, bronchospasm, hypoglycemia, bradycardia


Selective ß-1 antagonist


<15 min

0.25-0.5 mg/kg IV bolus, then 50-200 |g/kg/min

Bradycardia, congestive heart failure


Calcium channel antagonist

1 -5 min

3-6 hr

5 mg/hr IV, increase by 1-2.5 mg/hr q 15 min, up to 15 mg/hr

Hypotension, reflex tachycardia


Angiotensin converting enzyme inhibitor

5-15 min

6 hr

0.625-1.25 mg IV over 15 min

Renal dysfunction


a-2 receptor agonist


8-12 hr

0.1 mg orally q 12 h; up to 2.4 mg/day

Sedation, brady-cardia, rebound hypertension


a-1, a-2 receptor antagonist

2 min

10-15 min

5-20 mg IV

Tachycardia, arrhythmias


Activation of Gamma amino butytic acid receptor

2 min

5-10 min

30-60 mg IV

Myocardial depression


Dopamine-1, a-2 receptor agonist

15 min

10-20 min

0.01-1.6 |g/kg/min IV; no bolus

Tachycardia-bradycardia, hypokalemia


Ganglionic blockade


5-10 min

1-5 mg/min IV

Cycloplegia, mydriasis, urinary retention, bronchospasm


Adenosine receptor agonist

<1 min

1-2 min

Up to 220 mg/kg/min



Nitric oxide

1 -2 min

3-5 min

5-100 |g/kg/min

Methemoglobin production

Abbreviations: IV, intravenous; GABA, Gamma-aminobutyric acid; DA, Dopamine. Source: From Ref. 92.

Abbreviations: IV, intravenous; GABA, Gamma-aminobutyric acid; DA, Dopamine. Source: From Ref. 92.

and MABP was maintained at below 125 mmHg in the first 2 to 6 hr of presentation were associated with better outcomes in both mortality and severe morbidity (admission MABP: p < 0.005; 2-6 hr MABP: p < 0.005) (95). This study, however, did not adjust for variables, such as hematoma volume, ventricular blood, and initial GCS, which may have confounded the results. A different study reported an opposing result using serial MABP recordings over the first 24 hr after presentation in 105 patients with spontaneous ICH (96). Each patient's MABP was calculated as a slope, and the effect of MABP slope on mortality and functional outcome was determined, with adjustment for other predictive factors. The MABP slope (faster rate of decline) was significantly associated with increased mortality (p = 0.04), independent of initial GCS and hematoma volume (96) . The MABP slope, however, did not predict functional outcome among the survivors. The main explanation for this finding was thought to be a reduction in CPP, which worsened ischemic injury in the perihematoma zone, resulting in increased edema and mass effect by compensatory vasodilation in regions with intact autoregulation that exacerbated preexisting intracranial hypertension (95). Ohwaki et al. retrospectively studied associations of serial BP from admission to the second CT scan, with change in hematoma size in 76 patients with hypertensive ICH (97). Medical management attempted to lower SBP below targets of 140 to 170 mmHg. Hematoma enlargement (increase in volume >140% or 12.5 cm3 ) occurred in 16 patients (21%) and was significantly and independently associated with maximum SBP (OR, per mmHg: 1.04; 95% CI: 1.01-1.07) after adjusting for hematoma volume and GCS at admission. A target SBP of greater than or equal to 160 mmHg was significantly associated with hematoma enlargement, compared to patients with a target SBP of less than or equal to 150 mmHg (97). Although this retrospective study cannot conclude that increased BP caused hematoma enlargement, the authors conclude that efforts to lower SBP to below 150 mmHg may prevent hematoma enlargement.

The only randomized study that evaluated BP management reported better outcomes with BP control, although the lack of CT data in this early study compromises its validity (98). Qureshi et al. assessed the feasibility and safety of aggressive antihypertensive treatment in a multicenter prospective study of 27 patients with ICH and acute hypertension (99). The target was SBP less than 160 mmHg and DBP less than 90 mmHg within 24 hr of symptom onset. Hematoma expansion was documented in 9% of patients, and patients treated within 6 hr of symptom onset were more likely to be functionally independent, according to modified Rankin scale, compared to patients treated at between 6 and 24 hr (p = 0.03) (99).

Considering the combined risks of inadequate CPP as a consequence of aggressive control of elevated BP and rebleeding, which may be related to very high SBP, the American Heart Association guidelines recommend maintaining MABP to less than 130 mmHg in patients with a history of hypertension and CPP greater than 70 mmHg in patients with an ICP monitor (5,100). Finally, SBP less than 90 mmHg should be treated with vasopressor agents.

In the chronic phase, hypertension has been identified as a major risk factor for development of primary and recurrent ICH with an association that is stronger than that observed for isch-emic stroke (71,101). In the Systolic Hypertension in the Elderly Program study (102), the relative risk reduction with antihypertensive treatment for hemorrhagic stroke was 0.46 (95% CI: 0.21-1.02), compared to 0.63 (95% CI: 0.48-0.82) for ischemic stroke. The treatment effect was observed within the first year of treatment for hemorrhagic stroke but not until the second year for ischemic stroke. In the case of recurrent ICH, 74 patients with hypertensive ICH studied prospectively for a mean of 2.8 years were found to have significantly higher DBP in the recurrence group, compared to the nonrecurrence group (88 ± 8 vs. 82 ± 7 mmHg; p=0.04). Recurrence rates were 10.0% per patient year in patients with DBP more than 90 mmHg, compared with less than 1.5% per patient year in patients with lower DBP (p<0.001) (103).

In conclusion, BP is often significantly elevated during the acute period after ICH and returns spontaneously to baseline values after the first week. The best current guidelines for managing BP in ICH are those provided by the AHA Stroke Council and are based on nonrandomized retrospective and anecdotal studies. Although many physicians believe in a conservative approach to BP management in these patients due to concern for decreasing CPP and belief that hematomas stop active bleeding within minutes, it is likely that careful lowering of arterial pressure to at least below 180 mmHg will have therapeutic benefit in reducing hematoma expansion. Moreover, the data supporting exacerbation of secondary neuronal injury in perihematoma regions with lowering of BP are not well supported, at least for small- to moderate-sized hemorrhages. Instead, it has been postulated that regions of increased DWI are due to "metabolic suppression" rather than ischemia, the clinical effects of which remain unknown at this time (89,90). A large randomized, controlled study of lowering of acute BP in ICH would be needed to resolve much of the controversy surrounding this topic.

Although hypertension is a primary cause of SAH and ischemic and hemorrhagic stroke, BP management in these conditions remains a controversial subject. The optimal strategy likely differs across individual patients, depending on mechanism of injury and determinants of cerebral perfusion. The challenge remains to identify these factors in an efficient way to produce rational approaches to BP control.

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