New Intracerebral Hemorrhage Management Guidelines Expand Recommendations and Highlight Need for Further Research
Pub Date: Thursday, July 29, 2010
Author: Lauren H. Sansing, MD
Morgenstern LB, Hemphill JC 3rd, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010. Published online before print July 22, 2010. 10.1161/STR.0b013e3181ec611b.
The new American Heart Association/American Stroke Association (AHA/ASA) Guidelines for the Management of Spontaneous Intracerebral Hemorrhage  offers updated practical guidelines for the clinical care of patients with acute intracerebral hemorrhage (ICH). The authors are to be commended for incorporation of new clinical trial results and the multiple updates since the last guidelines were published in 2007. It is clear from reading the guidelines, however, that many important clinical questions remain unanswered by the available data and ongoing and future research on this devastating disease is needed.
The new guidelines begin with initial management considerations and highlight the high rate of early neurologic deterioration in these patients, especially in the first few hours after onset. An important addition is the consideration of emergent computed tomography (CT) angiography and/or contrast-enhanced CT to identify contrast within the hematoma, which may identify patients at particularly high risk of hematoma expansion.[3,4] However, prospective validation of these findings and any potential management implications remain areas of active research. Another addition is the consideration of advanced imaging to identify underlying lesions for patients with prodromal symptoms or unusual radiologic appearance of the ICH, including subarachnoid hemorrhage, unusual shape or location, significant early edema, or suggestion of a mass. Whether advanced imaging should be considered in all ICH patients is another active area of research, and results from ongoing studies [e.g., Diagnostic Utility of MRI in Intracerebral Hemorrhage (DASH)] may lead to revision in future editions.
Substantial additions were made to the guidelines on the management of patients with acquired or congenital coagulopathies. Patients with coagulation factor deficiencies or thrombocytopenia should receive emergent replacement therapy. Elevated international normalized ratio due to oral anticoagulation therapy should be reversed with intravenous vitamin K as well as replacement of vitamin K-dependent factors with fresh frozen plasma or prothrombin complex concentrates. Recombinant Factor VIIa (rFVIIa) alone is not recommended for warfarin reversal or for limiting hematoma growth in patients who are not coagulopathic because it may not restore coagulation after warfarin use in vivo  and is associated with thrombotic events. However, the efficacy and safety of rFVIIa-selected patients at high risk of hemorrhage expansion (e.g., noncoagulopathic patients with contrast extravasation within the hematoma on CT angiography) is currently being investigated in the Spot Sign for Predicting and Treating ICH Growth Study (STOP-IT). Antiplatelet medication use has not been consistently associated with hemorrhage expansion or poor outcome in prospective studies [7-11]; and thus, the benefit of platelet transfusions in these patients is unclear. However, the use of bedside platelet function assays to rationally select patients who may benefit from transfusion [12,13] is an intriguing hypothesis awaiting further study.
The recent results of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT)  and Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)  pilot trials confirmed the feasibility and safety of acute, aggressive blood pressure (BP) lowering in the first few hours after ICH onset. However, the efficacy of this approach in preventing hematoma enlargement and improving clinical outcome is awaiting the results of the ongoing larger clinical trials. Thus, the new guidelines have not changed the current BP management algorithm set forth in 2007, but importantly added the likely safety of acutely lowering the blood pressure of hypertensive patients presenting with systolic BP less than 220 mm Hg to goal 140 mm Hg. Other recommendations focus on improved medical management of the ICH patient including intensive care unit care, normoglycemia, and the use of antiepileptic medications in patients only with clinical or electrographic seizures. Prophylactic use of anti-epileptic drugs (AEDs) is no longer recommended, reflecting recent data suggesting potential harm. Recent studies have also raised awareness of the impact of orders to limit the aggressiveness of care [e.g., do not resuscitate (DNR) orders] on the clinical outcome prediction tools many clinicians use to counsel families [17,18], leading to a cycle of prophecy fulfillment. As a result, the new guidelines suggest early aggressive care for all patients and caution against using DNR orders to justify limiting medical and surgical interventions other than resuscitation after cardiac or respiratory arrest. Although there is still no proven treatment for ICH, ongoing trials of new therapeutics include the Dose Finding and Safety Study of Deferoxamine in Patients with Brain Hemorrhage (DFO in ICH) and the Safety of Pioglitazone for Hematoma Resolution In Intracerebral Hemorrhage (SHRINC), both which made the jump from bench to bedside in the last year and will hopefully inform future guidelines.
The role of surgical interventions is another area of rapidly changing guidelines due to ongoing research. New recommendations include the consideration of intracranial pressure monitoring in patients in coma or with evidence of herniation, significant intraventricular hemorrhage (IVH) or hydrocephalus with a goal cerebral perfusion pressure of 50 to 70 mm Hg and ventricular drainage for patients with hydrocephalus and a depressed level of consciousness. In addition, ongoing research will clarify the safety and efficacy of administering intraventricular recombinant tissue plasminogen activator (rt-PA) in patients with significant IVH [Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVH)]. Surgical evacuation of the hematoma continues to be controversial, with conflicting results likely due to difference in timing, methods of evacuation, and the characteristics of the patients enrolled. For most patients, the benefits of evacuation are uncertain. However, patients with cerebellar ICH with neurologic deterioration or hydrocephalus should be evacuated. In addition, subgroup analyses from the International Surgical Trial of Intracerebral Haemorrhage (STICH)  suggested patients with lobar ICH greater than 30 cc and within 1 cm of cortex may benefit from evacuation and that craniotomy may be preferred, leading to the new recommendation that these patients might be considered for evacuation. However, these results need to be confirmed by the ongoing STICH2 trial. Another trial is currently investigating the role of minimally invasive surgery with intrahematomal rt-PA to augment the degree of hematoma evacuation (MISTIE) and preliminary results reveal reasonable safety. The results of these two large trials will likely significantly change future recommendations for surgical management.
The important factors for recurrence of ICH are reviewed in the guidelines, including factors associated with cerebral amyloid angiopathy (lobar location, older age, presence of apolipoprotein E e2 or e4 alleles, and increased number of microbleeds on magnetic resonance imaging) and anticoagulation. Although the recommendation to avoid anticoagulation in patients with nonvalvular atrial fibrillation after lobar ICH (but consider anticoagulation for those patients with atrial fibrillation after deep ICH or antiplatelet therapy for any patient after ICH) is unchanged from the previous guideline, the additional risk factors mentioned above may offer additional insight into the choice of antithrombotic therapy (in patients with an indication for such therapy) after ICH. In addition, the guidelines added recommendations for aggressive management of hypertension and avoidance of heavy alcohol use in the prevention of recurrent ICH. Finally, a section on the importance of early, multidisciplinary rehabilitation for recovery after ICH was added. Hopefully future research on rehabilitation strategies will enhance our understanding of how to optimize recovery.
Overall the new guidelines offer practical recommendations for the optimal management of patients with acute ICH and highlight the areas of management for which data is currently limited. Hopefully the guidelines will inspire clinicians to offer aggressive and appropriate care to ICH patients and consider enrollment in the many ongoing clinical trials whenever possible.
- Morgenstern LB, Hemphill JC III, Anderson C, et al. AHA/ASA guidelines for the management of spontaneous intracerebral hemorrhage: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke. 2010.
- Davis SM, Broderick J, Hennerici M, et al. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology 2006;66:1175-1181.
- Wada R, Aviv RI, Fox AJ, et al. CT angiography "spot sign" predicts hematoma expansion in acute intracerebral hemorrhage. Stroke 2007;38:1257-1262.
- Goldstein JN, Fazen LE, Snider R, et al. Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage. Neurology 2007;68:889-894.
- Rosovsky RP, Crowther MA. What is the evidence for the off-label use of recombinant factor VIIa (rFVIIa) in the acute reversal of warfarin? Hematology 2008;2008:36-38.
- Mayer SA, Brun NC, Begtrup K, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2008;358:2127-2137.
- Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997;28:1-5.
- Roquer J, Rodriguez Campello A, Gomis M, et al. Previous antiplatelet therapy is an independent predictor of 30-day mortality after spontaneous supratentorial intracerebral hemorrhage. J Neurol 2005;252:412-416.
- Foerch C, Sitzer M, Steinmetz H, et al. Pretreatment with antiplatelet agents is not independently associated with unfavorable outcome in intracerebral hemorrhage. Stroke 2006;37:2165-2167.
- Broderick JP, Diringer MN, Hill MD, et al. Determinants of intracerebral hemorrhage growth: an exploratory analysis. Stroke 2007;38:1072-1075.
- Sansing LH, Messe SR, Cucchiara BL, et al. Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH. Neurology 2009;72:1397-1402.
- Naidech AM, Bassin SL, Bernstein RA, et al. Reduced platelet activity is more common than reported anti-platelet medication use in patients with intracerebral hemorrhage. Neurocrit Care. Epub April 21, 2009.
- Naidech AM, Bernstein RA, Levasseur K, et al. Platelet activity and outcome after intracerebral hemorrhage. Ann Neurol 2009;65:352-356.
- Anderson CS, Huang Y, Wang JG, et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol 2008;7:391-399.
- Qureshi AI, Palesch YY, Martin R, et al. Effect of systolic blood pressure reduction on hematoma expansion, perihematomal edema, and 3-month outcome among patients with intracerebral hemorrhage: results from the Antihypertensive Treatment of Acute Cerebral Hemorrhage Study. Arch Neurol 67:570-576.
- Messe SR, Sansing LH, Cucchiara BL, et al. Prophylactic antiepileptic drug use is associated with poor outcome following ICH. Neurocrit Care 2009;11:38-44.
- Becker KJ, Baxter AB, Cohen WA, et al. Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies. Neurology 2001;56:766-772.
- Hemphill JC III, Newman J, Zhao S, et al. Hospital usage of early do-not-resuscitate orders and outcome after intracerebral hemorrhage. Stroke 2004;35:1130-1134.
- Mendelow AD, Gregson BA, Fernandes HM, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 2005;365(9457):387-397.
-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association --