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NINDS: Stroke Proceedings: Broderick



Proceedings of a National Symposium on
Rapid Identification and Treatment of Acute Stroke
December 12-13, 1996

Guidelines for Medical Care and Treatment of Blood Pressure
in Patients with Acute Stroke

Joseph P. Broderick, M.D. 
University of Cincinnati Medical Center

Guidelines for medical care of stroke patients have been recently published by the American Heart Association (1). Treatment guidelines for patients with acute stroke include oxygen as well as treatment of concomitant congestive heart failure, arrhythmia, hyperglycemia, and elevated body temperature. Even though these recommendations are not based on data from controlled randomized trials, all of these treatments are safe, potentially helpful, and noncontroversial.

Treatment of blood pressure in acute stroke, however, is more controversial and is the focus of this paper. There are no randomized trials that provide data to support guidelines for treatment of blood pressure in acute stroke patients (1-3). Previous guidelines have been based on clinical observations, clinical studies of the autoregulation of cerebral blood flow in humans and animals, animal models of acute stroke, and current concepts concerning the pathophysiology of focal brain ischemia. Most recent guidelines have recommended minimal or no initial treatment of mild to moderately elevated blood pressure during the first several hours in patients with ischemic stroke (1-3) but more aggressive treatment of elevated blood pressure in patients with intracerebral or subarachnoid hemorrhage (1,4,5). Guidelines for treatment of elevated blood pressure in the setting of thrombolytic therapy for acute ischemic stroke are lacking.

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Ischemic Stroke

Minimal or no treatment of mildly to moderately elevated blood pressure during the first hours of ischemic stroke is supported by human and animal data. Because of the partial or complete loss of autoregulation in ischemic brain, cerebral blood flow in these regions depends almost entirely on the arterial blood pressure to maintain cerebral perfusion (6-8). The majority of patients who have an ischemic stroke have a history of hypertension with a higher baseline arterial blood pressure as well as a higher and more narrow range of autoregulation of cerebral blood flow (6,7). Most patients with ischemic stroke who have elevated blood pressure during the first several hours after stroke onset have a spontaneous decline in elevated blood pressure without antihypertensive medication (9). Thus, lowering of elevated blood pressure to normotensive levels in ischemic stroke patients may exacerbate brain ischemia and result in poorer patient outcome, particularly in previously hypertensive patients (1,6).

None of the animal or clinical studies convincingly support treatment of mild to moderately elevated blood pressure in patients with ischemic stroke. Supportive studies for treatment of elevated blood pressure in ischemic stroke are limited to animal models of induced severe hypertension in the setting of focal cerebral ischemia (10) and clinical studies of hypertensive emergencies. Excessive levels of hypertension can lead to disruption of the blood-brain barrier with resultant edema and brain injury in animal models of focal brain ischemia (11-13). In addition, pharmacologic lowering of elevated blood pressure is recommended in patients with ischemic stroke who have a suspected aortic dissection or myocardial infarction to avoid worsening these conditions.

Guidelines for treatment of blood pressure in the setting of ischemic stroke have been proposed and are listed in Table 1 . The agents used to treat elevated blood pressure should be easily titratable with a quick onset of action but with a limited risk of excessive and sudden lowering of blood pressure. Preferred agents include low doses of intravenous labetalol or low doses of enalapril. Some investigators have also used small patches of nitropaste. More aggressive, but also easily titratable, treatment of blood pressure includes continuous intravenous infusions of nitroglycerin, nitroprusside, or esmolol. Sublingual nifedipine is one of the most commonly used agents to lower blood pressure in the emergency department. However, it should be viewed as second-line therapy since its effect may be delayed, it is more difficult to titrate as compared to the intravenous medications, and its use can be associated with precipitous drops in blood pressure (14). If blood pressure is lowered in this setting, serial neurological examinations should look for signs of deterioration such as increasing weakness or a reduced level of consciousness. The presence of these findings should prompt consideration of more conservative control of blood pressure.

The approval of t-PA for the treatment of acute ischemic stroke complicates management of elevated blood pressure in stroke patients. In the randomized NINDS t-PA Stroke Study (15), patients were excluded from treatment with t-PA if their blood pressure was greater than 185 mm Hg systolic or 110 mm Hg diastolic or required aggressive treatment to reach these limits. The rationale for these blood pressure limits derived from the association of baseline elevated blood pressure and subsequent intracranial hemorrhage in the myocardial infarction studies of t-PA as well as the pilot NINDS study of t-PA in acute stroke. Aggressive treatment was not specifically defined prospectively in the protocol of the NINDS randomized study but was thought to include intravenous nitroprusside or repeated doses of labetalol, enalapril, or nifedipine. In addition, elevated arterial blood pressure was closely monitored and treated during the first 24 hours. Patients who had persistent elevations in systolic blood pressure of greater than 185 mm Hg or diastolic pressures of greater than 105 mm Hg were generally treated with small doses of intravenous antihypertensive medication to maintain the blood pressure just below these limits. Thus, treatment of elevated blood pressure in acute ischemic stroke in the setting of the NINDS t-PA Stroke Study differed slightly from guidelines for ischemic stroke patients in general (Table 1). It is likely that these guidelines will evolve as additional randomized studies of thrombolytic therapy are completed.

Although the focus of this paper is treatment of elevated blood pressure, proper treatment of low blood pressure in the setting of acute ischemic stroke is equally important (Table 1). Low blood pressure in an elderly stroke patient may reflect dehydration, arrhythmia, or diminished cardiac output. Treatment considerations should include intravenous boluses of normal saline, treatment of severe bradycardia with atropine, or slowing of rapid atrial fibrillation with digoxin or a calcium channel blocker. If these maneuvers are ineffective in raising the blood pressure, consideration should be given to pressor agents such as dopamine, if not contraindicated.

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Intracerebral Hemorrhage

Control of elevated blood pressure has never been shown to decrease the risk of ongoing or recurrent bleeding in patients with intracerebral hemorrhage (4). Nonetheless, we recommend treatment of moderate and severe elevations of blood pressure (systolic blood pressure of greater than 180 mm Hg or mean arterial pressure of greater than 130 mm Hg). The goal of treatment should be to lower the blood pressure to a mean arterial pressure of 100-130 mm Hg or to the low hypertensive range (e.g., systolic pressure of 140-160 mm Hg). Lower blood pressures may be poorly tolerated because the cerebral perfusion pressure (CPP) is dependent on the intracranial pressure (ICP) as well as the arterial blood pressure (ABP): (CPP = ABP - ICP). High levels of ICP require higher blood pressures to maintain a stable CPP. If an ICP monitor is in place, the goal should be to maintain the CPP at 70-100 mm Hg (4).

The antihypertensive medication should be an agent that is quick in onset and whose effect is easily titratable. Intravenous labetalol is an excellent choice for moderate levels of elevated blood pressure because it is fast-acting, titratable, and has no known adverse effect on either ICP or autoregulation of local cerebral flow. Intravenous enalapril is also an excellent choice because it has no known effect on ICP or autoregulation. For more severe elevations (e.g., diastolic pressures greater than 130 mm Hg) nitroprusside is recommended. Theoretically, nitroprusside can increase ICP because it is a cerebral arterial vasodilator. However, this potential negative effect has not been demonstrated in clinical use. Nitroprusside has the advantage of being the easiest medication to titrate. Calcium channel blockers, such as sublingual nifedipine, are less predictable, slower in onset, and can dilate cerebral arteries. They should be employed only as a second-line medication when the other medications cannot be used.

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Subarachnoid Hemorrhage

The treatment of blood pressure in patients with subarachnoid hemorrhage is controversial (5). In addition, management of blood pressure depends upon the timing of treatment as well as the status of aneurysm clipping. For example, prior to operative clipping of the ruptured aneurysm, elevated blood pressure is usually pharmacologically lowered to decrease the risk of rebleeding from the cerebral aneurysm. Yet no study has shown that treatment of elevated blood pressure reduces the risk of rebleeding. After clipping of the aneurysm, patients are often treated with induced hypervolemia and hypertension to decrease the ischemia associated with vasospasm.

Oral nimodipine is given at a dose of 60 mg every 4 hours orally or through a nasogastric tube to decrease the morbidity associated with vasospasm and subsequent brain ischemia. This agent will result in mild lowering of blood pressure. However, if blood pressure remains elevated prior to clipping of the ruptured aneurysm, despite treatment with nimodipine, we recommend treatment of elevated blood pressure as per the guidelines for intracerebral hemorrhage.

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Table 1. Algorithm for Emergency Treatment of Blood Pressure in Patients with Ischemic Stroke

1 Blood pressure obtained by automatic sphygmomanometer should be correlated with a manual blood pressure cuff reading.
2 If diastolic blood pressure > 140 mm Hg occurs on two readings 5 minutes apart, then start a continuous IV infusion of an antihypertensive agent such as sodium nitroprusside (0.5-1.0 mg/kg/min). Patients who fall into this category are not candidates for t-PA therapy even if other inclusion criteria are met.
3 If systolic blood pressure is > 220 mm Hg or diastolic blood pressure is 121-140 mm Hg or mean arterial blood pressure is > 130 mm Hg on two readings 20 minutes apart, then give an easily titratable antihypertensive medication such as labetalol at 10 mg IV over 1-2 minutes. The labetalol dose may be repeated or doubled every 10-20 minutes until a cumulative dose of 300 mg has been administered via this mini-bolus technique. After the initial dosing schedule, labetalol doses may be administered every 6-8 hours as needed. Labetalol is usually avoided in patients with asthma, cardiac failure, or severe cardiac conduction abnormalities. Enalapril (1.25 mg over 5 minutes and repeated every 6 hours or as needed) is an acceptable alternative, particularly in patients with congestive heart failure. Consider starting with 0.625 mg over 5 minutes in the elderly. IV esmolol or small patches of nitropaste are other options. Patients who require more than two doses of labetalol or other antihypertensive agents to decrease blood pressure to < 185 mm Hg systolic or 110 mm Hg diastolic are generally not candidates for thrombolytic therapy even if other criteria are met.
4 If systolic blood pressure is 185-220 mm Hg or diastolic blood pressure is 105-120 mm Hg, emergency therapy should be deferred in the absence of left ventricular failure, aortic dissection, or acute myocardial ischemia. Patients who are potential candidates for t-PA therapy but who have persistent elevations in systolic blood pressure of > 185 mm Hg or diastolic pressure of > 110 mm Hg may be treated with small doses of IV antihypertensive medication to maintain the blood pressure just below these limits. However, more than two doses of an antihypertensive agent to lower the blood pressure below these limits is a relative contraindication for thrombolytic therapy and should be discouraged.
5 If blood pressure is lowered by antihypertensive agents in the setting of acute stroke, serial neurological examinations should be performed to look for signs of deterioration such as increasing weakness or reduced level of consciousness.
6 In acute stroke patients with systolic blood pressure < 185 mm Hg or diastolic blood pressure < 105 mm Hg, antihypertensive therapy is usually not indicated.
7 Although there are no data to support a threshold for treatment of hypotension in stroke patients, we recommend treatment for signs of dehydration, blood pressure that is substantially below the expected level for a given patient (consider past history of hypertension, treated or untreated), or both. Therapeutic options should include IV fluids, treatment of congestive heart failure and bradycardia, and consideration of pressor agents such as dopamine.

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References

1. Adams H, Brott T, Crowell R, et al. AHA Medical/Scientific Statement--Guidelines for management of patients with acute ischemic stroke: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1994;25(5):1901-1914.

2. Powers W. Acute hypertension after stroke: The scientific basis for treatment decisions. Neurology 1993;43:461-467.

3. Lisk D, Grotta J, and Lamki L. Should hypertension be treated after acute stroke? A randomized controlled trial using single photon emission computed tomography. Arch Neurol 1993;50:855-862.

4. Broderick J, Brott T, and Zucarello M. Management of intracerebral hemorrhage. In: Batjer H, ed. Cerebrovascular Disease. Philadelphia: Lippincott-Raven; 1996:1-17.

5. Mayberg M, Batjer H, Dacey R, et al. AHA Medical/Scientific Statement--Guidelines for management of aneurysmal subarachnoid hemorrhage: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Circulation 1994;90(5):2592-2605.

6. Strandgaard S. Autoregulation of cerebral blood flow in hypertensive patients. Circulation 1976;53:720-727.

7. Strandgaard S, and Paulson O. Cerebral blood flow and its pathophysiology in hypertension. AJH 1989;2: 486-492.

8. Symon L, Branston N, and Strong A. Autoregulation in acute focal ischemia. An experimental study. Stroke 1976;7:547-554.

9. Broderick J, Brott T, Barsan W, et al. Blood pressure during the first minutes of focal cerebral ischemia. Ann Emerg Med 1993;22:1438-1443.

10. Drummond J, Oh Y-S, Cole D, et al. Phenylephrine-induced hypertension reduces ischemia following middle cerebral artery occlusion in rats. Stroke 1989;20:1538-1544.

11. Hatashita S, Hoff J, and Ishii S. Focal brain edema associated with acute arterial hypertension. J Neurosurg 1986;64:643-649.

12. Kogure K, Busto R, and Scheinberg P. The role of hydrostatic pressure in ischemic brain edema. Ann Neurol 1981;9:273-282.

13. Fenske A, Kohl J, Regli F, et al. The effect of arterial hypertension on focal ischemic edema: An experimental study. J Neurol 1978;219:241-251.

14. Grossman E, Messerli F, Grodzicki T, et al. Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies? JAMA 1996;276:1328-1331.

15. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-1587.

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National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892

Last updated May 17, 2011