ST. LOUIS—Moderate reductions in arterial pressure do not lower cerebral blood flow (CBF) in patients with small- to medium-sized intracranial hemorrhages (ICH), according to a new study by Michael N. Diringer, MD, and colleagues.[1] Whether it improves outcome in these patients, though, remains to be investigated.

ACUTE HYPERTENSION IN ICH: TO TREAT OR NOT TO TREAT?

“ICH patients are initially very hypertensive,” explained Dr. Diringer, an Associate Professor of Neurology and Neurological Surgery at Washington University School of Medicine in St. Louis. Because these acute elevations in mean arterial pressure (MAP) usually resolve within a few days, the best management approach remains unclear. Dr. Diringer, who is also Director of the Neurology/Neurosurgery Intensive Care Unit at Washington University, noted, “There’s a controversy as to whether [uncontrolled hypertension] could lead to more bleeding.”

Evidence to support this hypothesis is scant. “People haven’t really shown an effect on re-bleeding,” said Dr. Diringer. But given that the elevated blood pressure can lead to systemic complications such as cardiac ischemia or failure, a plausible argument can be made for administering an antihypertensive.

On the other hand, Dr. Diringer voiced the worry of those afraid to lower MAP in ICH patients: “Are you going to cause more brain injury?” He explained, “There’s the concern that lowering blood pressure could contribute to ischemia” by reducing CBF around a hemorrhage, a notion largely based on findings that rapidly lowering blood pressure can precipitate or even worsen ischemic strokes.[2]

But, he indicated, “The whole fear of ischemia [in ICH] is ill-founded,” because most ICH researchers have looked only at blood flow, not at actual biochemical evidence of ischemia. When he and his colleagues did examine a key biochemical measure—tissue oxygen consumption around the ICH clot—they found no evidence of ischemia: Because oxygen consumption was reduced more than was CBF, the oxygen extraction fraction was lowered, rather than increased, as occurs with ischemia.[3]

AUTOREGULATION OF CBF IN ICH?

Under normal conditions, changes in MAP over a wide range have little effect on CBF. In response to changes in cerebral perfusion pressure (CPP; the difference between pressure in arteries feeding the brain and venous back-pressure or intracranial pressure [ICP]), brain arterioles adjust diameter to keep blood flow constant. However, there is a limit to brain arterioles’ flexibility: In normal humans, this autoregulation fails when CPP drops below approximately 50 to 60 mm Hg.

Chronic hypertension in ICH patients can raise this lower limit by a variable amount. Further, if ICP is increased by the hematoma, it can be elevated beyond the range in which adjustments of arteriolar resistance can compensate for the drop in CPP.

Dr. Diringer remarked, “Prior studies showed that autoregulation can be lost in cases of trauma and ischemia,” prompting the researchers to investigate how well autoregulation holds up after ICH.

CBF BEFORE AND AFTER ANTIHYPERTENSIVES

“What we did was a short-term physiological study: We measured blood flow before and after a moderate reduction in blood pressure in ICH patients,” said Dr. Diringer. Six to 22 hours after symptom onset, positron emission tomography (PET) was used to examine CBF in 14 patients with ICH of 1 to 45 mL in size. The patients, whose MAPs ranged from 129 to 158 mm Hg (mean, 143 mm Hg), were then randomized to receive either nicardipine (n = 7) or labetalol (n = 7) intravenously; doses were titrated to lower MAP by about 15%. After the patients’ MAPs had stabilized for at least 10 minutes (the reductions in MAP ranged from 10% to 30% [mean, 16.7%]), PET scans were repeated.

Said Dr. Diringer, “We found that the blood flow is maintained,” indicating that autoregulation of CBF is intact in ICH patients treated for acute hypertension. There was no change in either global CBF or CBF within the region surrounding the clot (periclot CBF). Additionally, changes in MAP could not be correlated with alterations in either global or periclot CBF.

ICH SIZE, MAP DROP MUST BE MODERATE

“This was a modest reduction in MAP,” Dr. Diringer emphasized. Larger decreases can be detrimental; reductions in MAP of more than 20% have been shown to reduce CBF. Additionally, Dr. Diringer pointed out, “We didn’t study people with really large hemorrhages.” In all patients, hemorrhages were considered small to moderate in size. The authors cited research indicating that, in cases in which ICP is elevated by the presence of a large hematoma or hydrocephalus, the lower MAP limit for preserving autoregulation may shift upward.

While research points to the first four hours after ICH onset as crucial for intervention, Dr. Diringer argued pragmatically, “We basically studied patients as soon as would be feasible to treat them.” In the present study, PET scans were performed on patients at least six hours (average, 15 hours) after symptom onset. “We used to think that bleeding occurred for a finite time and then stopped, but it looks like bleeding can continue for six hours or so,” said Dr. Diringer. In general, of ICH patients who present within hours of symptom onset, about 30% to 40% show enlargement of the hemorrhage in the next few hours, he noted.

DOES NOT HURT; DOES IT HELP?

As the authors admit, evidence for the value of reducing MAP in ICH patients is scarce: An association between blood pressure on admission and occurrence of early re-bleeding has not yet been established. In animal models, increases in blood pressure may exacerbate cerebral edema, but this has not been shown in humans, and the role of edema in early damage is questioned. Although the jury is still out as to whether treating sudden elevations of MAP in ICH patients can reduce re-bleeding or other damage, the study shows that moderate treatment with antihypertensives is safe. “All we can say is that there’s no evidence that lowering blood pressure is helpful; we’ve just demonstrated that lowering it isn’t harmful,” Dr. Diringer remarked.

—Mimi Zucker, PhD

References
1. Powers WJ, Zazulia AR, Videen TO, et al. Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage. Neurology. 2001:57:18-24.
2. Fischberg GM, Lozano E, Rajamani K, et al. Stroke precipitated by moderate blood pressure reduction. J Emerg Med. 2000;19:339-346.
3. Zazulia AR, Diringer MN, Videen TO, et al. Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage. J Cereb Blood Flow Metab. 2001;21:804-810.

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