Acute Hypertension in Intracerebral Hemorrhage Pathophysiology and Management
Acute Hypertension in Intracerebral Hemorrhage Pathophysiology and Management
Incidence
Intra-parenchymal bleeding with or without extension into the ventricles and rarely into the subarachnoid space is recognized as spontaneous intracerebral hemorrhage (ICH). Among all strokes spontaneous ICH accounts for approximately 10–15% cases, either primary or secondary.1 Chronic hypertension is regarded as the leading cause of the primary ICH, followed by amyloid angiopathy.2 Vascular malformation, coagulation abnormalities or intracranial tumors accounts for most cases of secondary ICH. Incidence of ICH ranges from 10–20 cases per 100,000 population.3 The mortality from ICH within the first months ranges from 44% to 51% and at two years postictus from 56% to 61%.4-6
There have been many studies showing the elevation of the blood pressure after ICH.7-10 Qureshi et al.,11 in their large cross-sectional study, showed elevated systolic blood pressure (SBP) ≥140mmHg in 63% of stroke patients, and the proportion of the patients with ICH with elevated SBP ≥140mmHg were 75%. Prevalence of various blood pressure in ICH were as follows: SBP between 140 and 184mmHg was 50%; SBP between 185 and 219mmHg was 17%; and SBP >220mmHg was 3%. Blood pressure elevation has been associated with poor clinical outcomes including death and dependency.10 This has been demonstrated in retrospective review by Dandapani et al.,12 in which they reviewed 87 patients with ICH with marked elevation of blood pressure on admission. The group of the patients who had SBP higher than 140mmHg had a higher rate of mortality.
Pathological Process
In order to understand how chronic hypertension influences the dynamics of the cerebral autoregulation we have to first understand the normal autoregulation of the brain. The cerebral autoregulation is maintained at the level of arterioles, which vasoconstrict with increase in blood pressure and vasodilate with decrease in blood pressure.These changes in vessel diameter maintain normal CBF under a wide range of cerebral perfusion pressure (CPP). The range of normal autoregulation is considered to be between 50 and 150mmHg. In chronic hypertensive patients there is a shift in the curve to the right, and thus patients with chronic untreated hypertension are at an increase risk of ischemic injury with sudden decrease in the CPP below the lower limit of autoregulation. The exact reasoning behind the acute elevation of the blood pressure in stroke patients is not absolutely obvious; many different explanations have been put forward to define the acute elevation: first, it could be the reflection of the untreated hypertension;13 second, Cushing-Kocher response, which is a reaction from the compression of the brain stem;4,14 and third, abnormal sympathetic, parasympathetic activity, raised levels of circulating catecholamines15 and brain natriuretic peptide (BNP).16
Justification of Blood Pressure Management
The hematoma expansion as we know it is a dynamic process and usually progress for first 24 hours, with its peak expansion within first six hours.17-19 The relationship between the early elevated blood pressure with CBF changes and poor clinical outcome has been demonstrated in many studies and is illustrated below, but the relationship of elevated blood pressure with hematoma expansion is not clear, and it is also unclear whether the hematoma expansion occurs as a result of elevated blood pressure or is a consequence of that.20 It is not clear whether to treat hypertension acutely after ICH, as the reduction of the blood pressure on CBF is unclear. Animal studies have shown a transient decrease in the global CBF, especially in the perihematoma region, which was presumed to be secondary to compression effect on the microvasculature. 21,22 There is an impairment of the autoregulation in the perihematoma and, as a result, sudden decrease in the blood pressure can lead to the vasodilatation which can increase the intracranial pressure (ICP) lowering the CPP.23 In an animal study performed by Qureshi et al.,24 there was no change seen in the CBF, cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF) in dogs with elevation of ICP and MAP after ICH. Subsequent authors with the help of radiological studies have come up with the similar conclusion. Hirano et al.25 and Zazulia et al.26 have shown no ischemia in the periclot region by the use of positron emission tomography (PET), and Carhuapoma et al.27 have shown the same results with diffusion weighted image (DWI) in patients with acute ICH. From the above studies it is clear that there is no ischemia in the perihematoma. The toxic effects of the blood and its products in the perihematoma can lead to the decrease in the metabolism.21,28,29 The CBF and metabolic changes in the perihematoma evolves in three different phases (see Figure 1): • hibernation phase, which is seen during the first 48 hours, and is defined as a reduction in the CBF and metabolism in both ipsilateral and contralateral hemispheres; • reperfusion phase, which is observed within 48 hours to 14 days and consist of heterogeneous pattern, including areas of normal, hypo- and hyperperfusion; and • normalization phase, which is seen after 14 days, and consists of normal blood flow except in nonviable tissue.30 The above theory, based on the careful laboratory and clinical evaluation, lays ground for the relative safety of decreasing blood pressure during the hibernation phase.
1. Dennis MS, et al.,“Long-term survival after first-ever stroke: the Oxfordshire Community Stroke Project”, Stroke (1993);24(6):
pp. 796–800.
2. Foulkes MA, et al.,“The Stroke Data Bank: design, methods, and baseline characteristics”, Stroke (1988);19(5): pp. 547–554.
3. Giroud M, et al., “Cerebral hemorrhage in a French prospective population study”, J Neurol Neurosurg Psychiatry
(1991);54(7): pp. 595–598.
4. Qureshi AI, et al., “Spontaneous intracerebral hemorrhage”, N Engl J Med (2001);344(19): pp. 1450–1460.
5. Juvela S, “Risk factors for impaired outcome after spontaneous intracerebral hemorrhage”, Arch Neurol (1995);52(12): pp.
1193–200.
6. Lisk DR, et al., “Early presentation of hemispheric intracerebral hemorrhage: prediction of outcome and guidelines for treatment
allocation”, Neurology (1994);44(1): pp. 133–139.
7. Wallace JD, Levy LL,“Blood pressure after stroke”, JAMA, (1981);246(19): pp. 2177–2180.
8. Britton M, Carlsson A, de Faire U, “Blood pressure course in patients with acute stroke and matched controls”, Stroke
(1986);17(5): pp. 861–864.
9. Aslanyan S, et al.,“Effect of blood pressure during the acute period of ischemic stroke on stroke outcome: a tertiary analysis of the
GAIN International Trial”, Stroke (2003);34(10): pp. 2420–2425.
10. Willmot M, Leonardi-Bee J, Bath PM, “High blood pressure in acute stroke and subsequent outcome: a systematic review”,
Hypertension (2004);43(1): pp. 18–24.
11. Qureshi AI, Ezzedine MA, Nasar Abu, et al., “Acute Hypertension in 563,704 Adult Patients Presenting to the Emergency
Room with Stroke in the United States”, American Journal of Emergency Medicine (2007); In Press.
12. Dandapani BK, et al., “Relation between blood pressure and outcome in intracerebral hemorrhage”, Stroke (1995);26(1):
pp. 21–24.
13. Arboix A, et al., “Differences between hypertensive and non-hypertensive ischemic stroke”, Eur J Neurol (2004);11(10):
pp. 687–692.
14. Qureshi AI, et al., “Long-term outcome after medical reversal of transtentorial herniation in patients with supratentorial mass
lesions”, Crit Care Med (2000);28(5): pp. 1556–1564.
15. Cheung RT, Hachinski V, “Cardiac Effects of Stroke”, Curr Treat Options Cardiovasc Med (2004);6(3):
pp. 199–207.
16. Nakagawa K, et al.,“Plasma concentrations of brain natriuretic peptide in patients with acute ischemic stroke”, Cerebrovasc Dis
(2005);19(3): pp. 157–164.
17. Chen ST, et al., “Progression of hypertensive intracerebral hemorrhage”, Neurology (1989);39(11): pp. 1509–1514.
18. Kazui S, et al., “Enlargement of spontaneous intracerebral hemorrhage. Incidence and time course”, Stroke (1996);27(10):
pp. 1783–1787.
19. Kelley RE, et al.,“Active bleeding in hypertensive intracerebral hemorrhage: computed tomography”, Neurology (1982);32(8):
pp. 852–856.
20. Kazui S, et al., “Predisposing factors to enlargement of spontaneous intracerebral hematoma”, Stroke (1997);28(12):
pp. 2370–2375.
21. Nath FP, et al., “Effects of experimental intracerebral hemorrhage on blood flow, capillary permeability, and histochemistry”, J
Neurosurg (1987);66(4): pp. 555–562.
22. Bullock R, et al., “Intracerebral hemorrhage in a primate model: effect on regional cerebral blood flow”, Surg Neurol
(1988);29(2): pp. 101–107.
23. Mendelow AD, et al., “Intracranial hemorrhage induced at arterial pressure in the rat. Part 2: Short term changes in local cerebral
blood flow measured by autoradiography” Neurol Res (1984);6(4): pp. 189–193.
24. Qureshi AI, et al., “No evidence for an ischemic penumbra in massive experimental intracerebral hemorrhage”, Neurology
(1999);52(2): pp. 266–272.
25. Hirano T, et al., “No evidence of hypoxic tissue on 18F-fluoromisonidazole PET after intracerebral hemorrhage”, Neurology
(1999);53(9): pp. 2179–2182.
26. Zazulia AR, et al.,“Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage”, J Cereb Blood Flow Metab
(2001);21(7): pp. 804–810.
27. Carhuapoma JR, et al.,“Diffusion-weighted MRI and proton MR spectroscopic imaging in the study of secondary neuronal injury
after intracerebral hemorrhage”, Stroke (2000);31(3): pp. 726–732.
28. Yang GY, et al., “Experimental intracerebral hemorrhage: relationship between brain edema, blood flow, and blood-brain barrier
permeability in rats”, J Neurosurg (1994);81(1): pp. 93–102.
29. Nath FP, et al., “Early hemodynamic changes in experimental intracerebral hemorrhage”, J Neurosurg (1986);65(5):
pp. 697–703.
30. Qureshi AI, et al., “Cerebral blood flow changes associated with intracerebral hemorrhage”, Neurosurg Clin N Am
(2002);13(3): pp. 355–370.
31. Broderick JP, et al., “Guidelines for the management of spontaneous intracerebral hemorrhage: A statement for healthcare
professionals from a special writing group of the Stroke Council, American Heart Association”, Stroke (1999);30(4):
pp. 905–915.
32. Meyer JS, Bauer RB, “Medical treatment of spontaneous intracranial hemorrhage by the use of hypotensive drugs”, Neurology
(1962);12: pp. 36–47.
33. Qureshi AI, et al., “Pharmacologic reduction of mean arterial pressure does not adversely affect regional cerebral blood flow and
intracranial pressure in experimental intracerebral hemorrhage”, Crit Care Med, (1999);7(5): pp. 965–971.
34. Powers WJ, et al.,“Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage”, Neurology
(2001);57(1): pp. 18–24.
35. Qureshi AI, et al., “A prospective multicenter study to evaluate the feasibility and safety of aggressive antihypertensive treatment
in patients with acute intracerebral hemorrhage”, J Intensive Care Med (2005); 20(1): pp. 34–42.
36. Qureshi AI, et al.,“Treatment of acute hypertension in patients with intracerebral hemorrhage using American Heart Association
guidelines”, Crit Care Med (2006);34(7): pp. 1975–1980.
37. Qureshi AI, “Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH): Rationale and Design”, Neurocritical
Care (2007);. In Press.
38. Chobanian AV, et al.,“The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment
of High Blood Pressure: the JNC 7 report”, JAMA, (2003);289(19): pp. 2560–2572.
