Brain Hemorrhage
Clarissa Chan, PharmD
In July, the American Stroke Association released the 2022 guideline for the management of spontaneous intracerebral hemorrhage (ICH) with recommendations for the acute management of ICH.
“ICH has one of the highest case-fatalities among all strokes and often outcomes depend on disease progression and management in the first 24 to 48 hours,” said Daniel Atashsokhan, MD, a PGY-2 in the department of neurology at State University of New York (SUNY) Downstate Medical School/One Brooklyn Health Program in New York, who was not involved with the guideline writing. “Therefore, it requires a system-based approach with multidisciplinary coordination between stroke, neurocritical care, and neurointerventional and neurosurgical services that focus on early and aggressive management.”
The key is preventing hematoma expansion—especially in the first 48 hours—due to high correlation with poor outcomes, said Ambooj Tiwari, MD, MPH, a neurointerventional surgeon and vascular neurologist in the department of neurology at New York University (NYU) Grossman School of Medicine, who also was not involved with the guidelines. Hematoma expansion depends on two specific aspects of management: coagulopathy disease-related control or pharmacological reversal and BP control.
Emergent anticoagulation reversal is crucial
In applicable cases, emergent anticoagulation or pathological coagulopathy reversal is often the target of hyperacute therapy in the first 60 minutes. For patients on coumadin, 4-factor prothrombin complex concentrate (4F PCC) and Vitamin K is preferred for reversal. The treatment goal is to reverse INR < 1.3 within the first 4 hours. Although typical dosing is 25–50 IU/kg, some studies have used 1,500 IU fixed dose regimens. If INR < 2.0, lower doses of 10–20 IU/kg are recommended.
Due to time cost, obtaining blood tests to confirm INR levels is not recommended, but using recent dosing to determine reversal need is advocated, said Tiwari. If agents were taken within two hours of presentation, activated charcoal can be used.
For patients on direct thrombin inhibitors like dabigatran or Factor Xa inhibitors, appropriate reversal agents include idarucizumab and andexanet alfa, respectively. When unavailable, the guideline recommends using 4F PCC.
In patients on heparin or low molecular weight heparins (LMWH), like enoxaparin, the guidelines recommend reversal with protamine. The guidelines did not find any advantage of reversing antiplatelet activity in those taking aspirin or adenosine disphosphate (ADP) receptor inhibitors, although use of platelet transfusion was reasonable in those taking the former—especially when an evacuation or craniotomy is planned, said Tiwari. Ciraparantag is a new potential universal antidote for anticoagulants.
BP control is critical
Another major aspect of limiting hematoma expansion is BP control. Based on data from two major trials (INTERACT2 and ATACH-2) on early intensive BP lowering, the guidelines’ recommended target for patients presenting with initial systolic BP (SBP) between 150–220 mm Hg is to reduce their BP to within 130–140 mm Hg over 4.5–6 hours.
“Ultra-aggressive lowering below that range or within the first 2 hours seems to lead to worse outcomes as well as cause acute renal injury,” said Tiwari. “The [guideline] authors felt that a reduction of 20 to 40 mm Hg in the first hour seemed to be the most reasonable approach.”
For patients presenting with SBP > 220 mm Hg, a threshold of SBP lowering within 90 mm Hg was best in order to avoid acute renal injury, said Tiwari.
Most importantly, the research team found significant variability in SBP control in the acute phase can lead to poor outcomes.
Therefore, the guidelines recommend antihypertensive agents with rapid onset and short duration of action to facilitate titrability.
“There are large knowledge gaps remaining as to which agents to select and whether to administer as bolus versus drip,” said Steven Greenberg, MD, PhD, director of the Hemorrhagic Stroke Research Program at Massachusetts General Hospital and professor of neurology at Harvard Medical School in Boston, MA, who was involved in the ICH guideline updates.
Hematoma expansion management
Most postemergent acute care involves hematoma expansion management in the first 48 hours and related complications like aspiration, infections, and cardiac arrythmias.
“If the hematoma has stabilized over serial CTs in 48 hours, the guideline recommends starting DVT prophylaxis with heparin or low molecular weight heparin within 48–96 hours since ICHs have a 7% incidence of thromboembolic complications,” said Tiwari. “Studies found that pharmacological prophylaxis with or without intermittent pneumatic compression was superior to compression stockings.” ■