The New ICH Guidelines –Significant Advances, Inclusion of Long Standing Practices, and Awaiting Further Data

The management of blood pressure, the need for surgical intervention, the approach to anticoagulant reversal and the timing of anticoagulant restart are the most pressing decisions in the management of spontaneous intracerebral hemorrhage (ICH). The current revised guidelines include several important revisions based on recent evidence and evolving consensus. Few of the most important decisions are based on unambiguous recommendations to treat (Class I) or not to treat (Class III), and fewer still are based the highest level of evidence (Level A). Considerations of the newer oral anticoagulants are included in this guideline revision for the first time, and little data has yet to be amassed. Expert consensus opinion plays an influential role in the recommendations. This commentary will highlight the new or revised recommendations that have emerged since the 2010 Guideline for the Management of Spontaneous ICH.

Blood Pressure Control

It has been well established that long term control of blood pressure reduces the risk of recurrent ICH. Thus, blood pressure should be well controlled after ICH in all patients. The current Guideline offers a new recommendation of target blood pressure control to less than 130/80 (previous recommendation was less than 140/90). The question of the timing and aggressiveness of blood pressure lowering has been the subject of recently completed and ongoing clinical trials. Historical concerns that acute blood pressure lowering may exacerbate cerebral injury were based on the idea that an ischemic penumbra surrounding the hematoma may progress to permanent cerebral injury if blood pressure is lowered too much or too rapidly. However, brain imaging studies have suggested that perihematomal ischemia is not typical of ICH, and if present, not clinically significant. The latter conclusion was reinforced by the INTERACT2 trial, a randomized trial demonstrating that rapid systolic blood-pressure lowering to less than 140 mm Hg in patients with acute ICH less than 6 hours from onset and systolic blood pressure between 150 and 220 mm Hg did not result in a higher proportion of bad outcomes at 90 days (the primary analysis) compared to the control group lowered to less than <180 mm Hg. On the contrary, a secondary analysis showed a significant benefit on the modified Rankin scale. The current Guideline now recommends that measures to control blood pressure should begin immediately after ICH onset and that rapid lowering of blood pressure as performed in the INTERACT2 is safe and may be beneficial. A further, new recommendation, based on Level C evidence is that for ICH patients presenting with systolic BP above 220 mm Hg, it may be reasonable to consider aggressive reduction of blood pressure with a continuous intravenous infusion and frequent blood pressure monitoring.

Surgical Management

With regard to surgical treatment of ICH, the new Guideline adds additional clarifications of circumstances when surgery may or may not be reasonable for supratentorial ICH. As lifesaving measures, hematoma evacuation in deteriorating patients might be considered, and decompressive craniectomy with or without hematoma evacuation might be considered for patients who are in coma, have large hematomas with significant midline shift, or have elevated intracranial pressure refractory to medical management. Early hematoma evacuation is not clearly beneficial compared to hematoma evacuation when patients deteriorate. The effectiveness of minimally invasive clot evacuation utilizing stereotactic or endoscopic aspiration with or without thrombolytic usage is uncertain and currently the subject of clinical trials.

Anticoagulant Associated

ICH Recent evidence from a randomized comparison of a 4-factor prothrombin complex concentrate (PCC) in patients on vitamin K antagonists (e.g., warfarin) to fresh frozen plasma (FFP) demonstrated a more rapid reversal of the elevated INR and fewer complication the 4-Factor PCC compared to plasma as has led to the new recommendation that 4-factor PCC might be considered over FFP for vitamin K antagonist reversal in ICH. Enthusiasm for the advantages of the new oral anticoagulants (NOACs) dabigatran, rivaroxaban, and apixaban, have been tempered by the lack of a specific antidote and little data related to the reversal of their effects. For patients with ICH who are taking dabigatran, rivaroxaban or apixaban, expert consensus suggests that treatment with factor VIII inhibitor bypassing activity, other PCCs or recombinant factor VIIa might be considered on an individual basis. Activated charcoal might be used if the most recent dose of dabigatran, apixaban or rivaroxaban was taken less than 2 hours previous. Hemodialysis might be considered for dabigatran. Specific reversal agents for the NOACs are being developed and are in trial. It is expected these antidotes may become available for use within the next few years.

Anticoagulation and Antiplatelet Therapy Following ICH In patients with a strong indication for anticoagulation or antiplatelet therapy to prevent ischemic events, a trade-off with increasing the risk of recurrent ICH must occur. However, the optimal timing of initiating this therapy following ICH is unknown. The new, current recommendation is to wait at least 4 weeks in patients without mechanical heart valves before resuming oral anticoagulation. However, aspirin monotherapy may be started within days after the ICH. Although in the ischemic stroke prevention trials, NOACs seemed to cause fewer ICH than warfarin in patients with atrial fibrillation, it is uncertain whether their risk of recurrent ICH is less than warfarin.

Overdue Recommendations

Several ICH management practices long in use are addressed in the revised Guideline as recommendations for the first time: Corticosteroids should not be administered for treatment of elevated intracranial pressure in ICH. Protamine sulfate may be considered to reverse heparin in patients with acute ICH. Treatment of fever after ICH may be reasonable. Initial monitoring and management of ICH patients may take place in a dedicated stroke unit with physician and nursing neuroscience acute care expertise, as an alternative to an intensive care unit. The consideration of these management issues add to the thoroughness and utility of the Guidelines as a resource for Stroke centers and providers.

What might we expect in the next revision of the AHA ICH Guidelines and hope for to improve prevention and management of ICH? More evidence on the role, risks, and reversal for the NOACs in ICH is expected to greatly add to our knowledge base over the next three years. The ATACH II trial will report out and may strengthen or weaken the argument for rapid lowering of blood pressure to normal levels in acute ICH. We await the results of the MISTIE III and CLEAR III trials on whether minimally invasive endoscopic surgery of hematoma or IVH evacuation with tPA is beneficial.