Jun 212013

image: Wikipedia
Rapid Blood Pressure Control Doesn't Hurt, May Help in Intracerebral Hemorrhage

Strokes caused by intracerebral hemorrhage -- sudden bleeding into the brain -- are as devastating as they sound. Almost half of people with intracerebral hemorrhage (ICH) die within a month, and most of the survivors end up in nursing homes or needing full-time care at home.

These strokes are partially caused by high blood pressure, and blood pressure goes up after intracerebral hemorrhage often to shocking levels (200/120 is a not-uncommon value). A debate has simmered around this phenomenon: does this acute hypertension represent an adaptive (helpful) response by the body, pushing blood up into the brain where it's needed? Or does high blood pressure during an intracerebral hemorrhage make everything worse, justifying immediate normalization of the blood pressure?

Most doctors' response to this conundrum has been to split the difference, by following the American Heart Association's guidelines' target mean arterial pressure of < 110 mm Hg or BP < 160/90, absent evidence of decreased cerebral perfusion pressures (MAP < 130 if increased intracranial pressure or decreased cerebral perfusion pressure are present). And further, many internal medicine-trained physicians tend to bring BP down slowly, over a day or 2, having been taught rapid BP correction can worsen outcomes in intracerebral hemorrhage and hypertensive emergencies.

However, as usual, the reality isn't so clear:

  • The INTERACT trial showed rapidly lowering blood pressure reduced hematoma growth over 72 hours in patients with intracerebral hemorrhage, without apparently hurting anyone (n=404 patients).
  • The ATACH trial rapidly reduced or normalized blood pressures, and found it wasn't harmful (n=60 patients).

This month in the New England Journal of Medicine, the long-awaited INTERACT2 trial was published -- a much larger study whose findings were expected to dwarf the previous data in importance.

What They Did

Authors randomized 2,839 patients who had just had an intracerebral hemorrhage (<6 hours) to either:

  • Have their blood pressure nearly-normalized (<140 SBP) over one hour, and maintained there for 7 days, or
  • Standard treatment with the goal of SBP < 180 mm Hg.

The primary outcome was death or major disability (Rankin score 3-6).

What They Found

People who got rapid blood pressure reduction did no worse and appeared to do better, with 52% experiencing death or severe disability, compared to 56% in the standard care group. This finding was just barely non-significant with a confidence interval of 0.75 to 1.01, p=0.06. Also,

  • When authors re-ran the numbers with an ordinal analysis (as opposed to the binary primary outcome / no primary outcome analysis), it appeared that intensive blood pressure reduction improved functional outcomes, with an odds ratio of 0.87 for greater disability (0.77 to 1.00 with p=0.04). Clinical researchers like ordinal analyses for their inherently higher power to show an effect, compared to binary analyses.
  • Mortality was identical between groups at 12%.
  • Serious adverse events occurred in 23% in both groups.

Important caveat: Almost 70% of the subjects were in China, a very different society and health care system. The most-often used antihypertensive drug was urapadil, an intravenous alpha-adrenergic anatagonist also available in Europe, but not in the U.S.

What It Means

Another piece of dogma -- "we must reduce blood pressure cautiously and incompletely to avoid worsening brain ischemia in patients with intracerebral hemorrhage" -- bites the dust in the wake of this large, well conducted clinical trial. INTERACT2 may not immediately establish a new standard of care, but it should improve care overall by freeing physicians and nurses from the burden of micromanaging the blood pressure in patients with intracerebral hemorrhage, which is probably unnecessary (assuming the maintenance of cerebral perfusion pressure is at least being considered).

Early adopter intensivists will jump into use of this treatment based on the encouraging outcomes data, as well as its safety, and this seems wholly reasonable. It will be interesting to see what leading academic neurocritical care units do -- leave this up to attendings' personal styles, or endorse it by baking it into unit protocols.

Interestingly, the possible benefit seen in the first INTERACT -- reduced growth of hematoma -- didn't show up here, so the mechanism of any benefit from early rapid reduction of blood pressure in intracerebral hemorrhage remains unknown. The ongoing ATACH II trial testing intensive blood pressure lowering in ICH should eventually provide more helpful information. ATACH II is being conducted in North America, and limits antihypertensive treatment to nicardipine, making its results more applicable to U.S. practice.

takeawayClinical Takeaway: Contrary to convention, rapidly lowering blood pressure to near-normal levels seems safe, possibly even helpful, in patients with intracerebral hemorrhage and severe hypertension. Physicians who choose not to pursue this practice just yet can worry less about fluctuations in blood pressure in their intracerebral hemorrhage patients receiving intravenous antihypertensive drips.

Craig S. Anderson and the INTERACT2 investigators. Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage. N Engl J Med 2013; 368:2355-2365.

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In intracerebral hemorrhage, rapid blood pressure reductions were safe (INTERACT2)