New treatments for brain hemorrhage

May 4 2007

The first scientifically proven treatments for intracerebral hemorrhage, or "bleeding," strokes, are on the horizon, including a new drug that holds promise for slowing bleeding and limiting brain damage resulting from such a stroke, according to updated American Heart Association/American Stroke Association guidelines.

The guidelines, published in Stroke: Journal of the American Heart Association, also address the feasibility and timing of surgical options and different ways to take pictures of the brain to diagnose a hemorrhagic stroke, as well as offer guidance on end-of-life issues such as putting "do-not-resuscitate" orders on hold for a full day after such a stroke occurs.

Intracerebral hemorrhage (ICH) is a stroke caused when a defective artery in the brain bursts, flooding the surrounding tissue with blood. ICH accounts for less than 10 percent of first-ever strokes, with 35 percent to 52 percent of patients dying within a month. Of the estimated more than 60,000 patients who have an ICH in a year, only 20 percent are expected to be functionally independent six months afterwards.

Reducing high blood pressure is still the best way to avoid ICH, said Joseph Broderick, M.D., chair of the guideline writing committee and professor and chairman in the neurology department of the University of Cincinnati.

"ICH is the second most common type of stroke and its incidence is staying the same or slightly increasing," he said. "The time is right for updating the guidelines because there have been a number of published studies that may affect how we manage these very sick patients."

When the AHA/ASA published guidelines for managing ICH in 1999, researchers had conducted only five small, randomized medical studies and four small, randomized surgical trials for acute ICH. In the past six years, 15 pilot and larger randomized medical and surgical trials for ICH/intraventricular hemorrhage (IVH) have been completed or are ongoing.

Surgery

Since the last Guidelines for Management of ICH were published, researchers have completed the largest ever surgical trial of intracerebral hemorrhage, Broderick said.

"We have a better understanding of when and when not to use surgery but we still need more trials," he said. "We don't recommend routine surgical treatment of ICH, but people who have larger blood clots close to the surface of the brain may be an exception."

Surgery is recommended as a potentially life-saving procedure for patients with a larger ICH in the cerebellum that presses upon the brainstem.

Broderick said minimally invasive ways to remove blood clots are under investigation.

Medical Treatment of Acute ICH

Patients with an ICH should be managed in a hospital with an intensive care unit experienced in the management of patients with ICH, including neurosurgical expertise.

Recombinant activated factor VII (rFVIIa) is a drug that slows down bleeding and is approved to treat bleeding in patients with hemophilia. The new guidelines suggest using this drug in ICH patients within four hours after the onset of ICH limits the amount of bleeding and may reduce death and improve a patient's functional outcome at 90 days.

"rFVIIa is mentioned as a potential new treatment that needs confirmation," Broderick said. "The efficacy and safety of this treatment must be established in an ongoing phase III trial before its use in patients with ICH can be recommended outside of a clinical trial."

rFVIIa may also be a way to treat patients taking the blood-thinner warfarin when they have an ICH. Clinical trials to replace clotting factors using different approaches in these patients are also in planning stages.

Marked elevation of blood pressure is commonly seen in patients with ICH, but the ideal level of blood pressure control in the first hours after ICH has not yet been identified in previous clinical studies and trials. The current guidelines provide some suggested approaches, but ongoing clinical trials of acute blood pressure management will likely modify and/or clarify these recommendations in the future.

Imaging

"There's been more research into how we take pictures of the brain in patients with suspected ICH," Broderick said. Computed tomography (CT) and magnetic resonance (MR) scans appear equal in the ability to identify the ICH, its size and location and ongoing bleeding, according to the updated guidelines.

"Before, a CT scan was the primary option for evaluating stroke patients in an emergency. Data now show that MR scans also do the job and both are first-choice options," Broderick said.

Each type of imaging has benefits: CT may be superior at showing associated ventricular extension, while MR is superior at detecting underlying structural lesions in the brain. MR is also better than CT at showing tiny old hemorrhages in the brain. However, MR is not always as practical as the faster CT scan for patients who are unconsciousness, vomiting or on a ventilator. In patients with contraindications to MR, such as those with pacemakers, CT should be obtained. End-of-Life Concerns

Due to high death rates associated with ICH, the writing committee advises early discussion of withdrawal of care and end-of-life issues. "This is the first time the guidelines try to address how and when physicians should discuss ,do-not-resuscitate (DNR), orders," Broderick said.

A hemorrhagic stroke is a devastating event. DNR orders are extremely common in ICH and withdrawing life-sustaining support is the most common immediate cause of death in the patients. The guidelines note this may falsely lead to the belief that outcome from ICH is universally bleak.

Therefore, the AHA/ASA recommends carefully considering aggressive full care during the first 24 hours after an ICH, including all appropriate medical and surgical interventions, and that the establishment of new DNR orders be postponed during that time. Patients with previously established DNR orders are not included in this recommendation.

Prevention and Recognition

Treating high blood pressure remains the most important target for preventing ICH. Smoking cigarettes, heavy alcohol use and cocaine , risk factors for ICH , should be discontinued to prevent recurrent ICH.

As with any stroke, recognizing the symptoms and seeking treatment quickly affect the extent of brain damage as well as chances of survival. The symptoms of stroke include:

• Sudden numbness or weakness of the face, arm or leg, especially on one side of the body
• Sudden confusion, trouble speaking or understanding
• Sudden trouble seeing in one or both eyes
• Sudden trouble walking, dizziness, loss of balance or coordination
• Sudden, severe headache with no known cause

Headache and vomiting are more common with ICH than with other types of stroke, according to the guidelines.

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