Physician's Weekly Article - Treatment Advice for Adult Brain Hemorrhage

       Updated recommendations for spontaneous intracerebral hemorrhage address emerging drug therapies, surgical considerations, and end-of-life issues in this patient population.

      Intracerebral hemorrhage (ICH) continues to be a devastating medical and socioeconomic problem in the United States, accounting for 10% to 15% of all first-ever strokes each year. ICH is associated with a 30-day mortality rate ranging between 35% and 52%. In 2007, the American Heart Association (AHA) and the American Stroke Association (ASA) updated evidence-based guidelines for the management of spontaneous ICH in adults to provide physicians with more current and comprehensive recommendations on diagnosis and treatment. Published in the May 2007 issue of Stroke, the guidelines incorporate findings from significant medical trials that have occurred since the original guidelines were released in 1999.

      Brain Imaging Advances

      ICH is considered a medical emergency that should be promptly recognized and diagnosed. According to Joseph P. Broderick, MD, FAHA, who chaired the new AHA/ASA guidelines, brain imaging is a crucial part of initial evaluation. “Brain CTs have been the standard diagnostic tool to determine the presence of an ischemic or intracerebral stroke,” he says “Data from recent studies suggest that CT and MRI appear to identify the presence of ICH, size and location, and hematoma enlargement equally. CT and MRI are now advised as first-line diagnostics to differentiate between hemorrhage into the brain and ischemic infarcts.” MRI is superior to CT in identifying tiny remote brain hemorrhages and in delineating the amount of perihematomal edema. Additionally, non-contrast MRI may be superior to CT to spot associated vascular malformations, especially cavernomas, and to detect underlying structural lesions. However, the guidelines note that CT may be better than MRI for deciphering associated ventricular extension; CT is also considered a more practical imaging test for all presenting patients.

      Medical & Surgical Approaches

      The new recommendations for acute ICH clarify strategies to control elevated blood pressure, including the use of intravenous medications. However, the ideal level of blood pressure control in the first hours after ICH has yet to be identified. The new guidelines provide some suggested approaches, but future studies are necessary. “Long-term control of hypertension remains a primary target for prevention of ICH and recurrent ICH,” says Dr. Broderick.

      Treatment with recombinant activated factor VII (rFVIIa) within the first 3 to 4 hours after ICH onset slowed bleeding progression in a recent phase II trial and a phase III Trial (Table 1). However, Dr. Broderick notes that the clinical benefit of rFVIIa that was suggested in the phase II trial was not replicated in the phase III trial. He cautions that efficacy and safety of rFVIIa must be confirmed in future phase II and III trials, and should not be considered part of current standard practice.

      Data from randomized trials on the efficacy of surgery for ICH are lacking, resulting in substantial variability in surgical management. Dr. Broderick says the International Surgical Trial in Intracerebral Hemorrhage trial, or STICH (published in January-February 2005 issue of the Lancet), represents an important milestone in the role of surgical treatment for ICH. “Findings from the STICH trial significantly influenced the updated recommendations on surgical approaches,” says Dr. Broderick. “Results revealed no significant differences in outcomes between patients who had surgery and initially conservative treatment. As such, the AHA/ASA guidelines do not recommend routine evacuation of blood clots by standard craniotomy within 96 hours.”

      Conversely, the guidelines do recommend that patients with cerebellar hemorrhages larger than 3 cm who are deteriorating neurologically or who have brain stem compression and/or hydrocephalus from ventricular obstructions undergo surgical removal of the hemorrhage as soon as possible (Table 2). Dr. Broderick notes that the subgroup of patients with an ICH near the surface of the brain in the STICH trial appeared to benefit from early surgery. An ongoing randomized study is now examining patients with bleeding near the surface of the brain to determine whether surgery or best medical therapy available would optimize outcomes.

      DNR Considerations

      Unlike earlier guidelines for spontaneous ICH, the new recommendations address considerations for using early do-not-resuscitate (DNR) orders and the withdrawal technological support. “ICH patients are typically in poor condition and may appear to have no likely recovery after disease onset,” says Dr. Broderick. “Although a DNR order means that aggressive treatment should not occur in the event of cardiopulmonary arrest, in practical use, it’s associated with an overall lack of aggressiveness of care. In some respects, it can be a self-fulfilling prophecy. Several studies suggest that early DNR orders were predictive of patient death, independent of clinical characteristics. Therefore, the new AHA/ASA guidelines recommend aggressive care for all patients during the first 24 hours of ICH onset and postponement of new DNR orders during that time.” He added that patients with previous DNR orders were not included in the recommendation.

      Joseph P. Broderick, MD, FAHA has indicated to Physician’s Weekly that he has been on the speakers’ bureau or received honoraria from Boehringer Ingelheim. He has also worked as a consultant or is on the advisory board for Genentech and Novo Nordisk (Clinical Trial Steering Committee).