Surgical techniques
Post hoc subgroup analyses of the STICH (Surgical Trial in Intracerebral Haemorrhage) trial suggested a benefit for resection of haematomas <1 cm from the brain surface and possible harm from resection for patients in coma (Glasgow Coma Scale ≤8).[102]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 Jan 29-Feb 4;365(9457):387-97.
http://www.ncbi.nlm.nih.gov/pubmed/15680453?tool=bestpractice.com
Some data support the possibility of a good outcome with early resection (<12 hours), despite a possible higher rate of recurrent bleeding.[23]Greenberg SM, Ziai WC, Cordonnier C, et al. 2022 Guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association. Stroke. 2022 Jul;53(7):e282-361.
https://www.ahajournals.org/doi/full/10.1161/STR.0000000000000407
http://www.ncbi.nlm.nih.gov/pubmed/35579034?tool=bestpractice.com
Extensive research is being done to assess the benefit of haematoma drainage through minimally invasive surgery. An extensive meta-analysis showed that patients with supratentorial intracerebral haemorrhage (ICH) may benefit from minimally invasive draining techniques, especially when suffering superficial 25 mL to 40 mL haematomas.[103]Zhou X, Chen J, Li Q, et al. Minimally invasive surgery for spontaneous supratentorial intracerebral hemorrhage: a meta-analysis of randomized controlled trials. Stroke. 2012 Nov;43(11):2923-30.
https://www.ahajournals.org/doi/full/10.1161/strokeaha.112.667535
http://www.ncbi.nlm.nih.gov/pubmed/22989500?tool=bestpractice.com
The phase 2, randomised, controlled, open-label MISTIE trial showed that minimally invasive surgery plus alteplase appears to be safe in patients with ICH; however, increased asymptomatic bleeding was a major finding.[104]Hanley DF, Thompson RE, Muschelli J, et al. Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial. Lancet Neurol. 2016 Nov;15(12):1228-37.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154627
http://www.ncbi.nlm.nih.gov/pubmed/27751554?tool=bestpractice.com
The STICH II trial confirmed that early surgery of superficial haemorrhage may offer a small survival advantage, especially in the non-comatose group of patients that present with or progress to a decreased level of consciousness (Glasgow Coma Score 9 -12).[105]Mendelow AD, Gregson BA, Rowan EN, et al; STICH II Investigators. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet. 2013 Aug 3;382(9890):397-408.
http://www.ncbi.nlm.nih.gov/pubmed/23726393?tool=bestpractice.com
The ICES study also showed that early intraoperative stereotactic computed tomography (CT)-guided endoscopic surgery is a safe and effective method to remove acute ICHs.[106]Vespa P, Hanley D, Betz J, et al. ICES (intraoperative stereotactic computed tomography-guided endoscopic surgery) for brain hemorrhage: a multicenter randomized controlled trial. Stroke. 2016 Nov;47(11):2749-55.
https://www.ahajournals.org/doi/full/10.1161/strokeaha.116.013837
http://www.ncbi.nlm.nih.gov/pubmed/27758940?tool=bestpractice.com
The use of recombinant tissue plasminogen activator (r-TPA) has been shown to accelerate resolution of intraventricular haemorrhage.[107]Webb AJ, Ullman NL, Mann S, et al. Resolution of intraventricular hemorrhage varies by ventricular region and dose of intraventricular thrombolytic: the Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) program. Stroke. 2012 Jun;43(6):1666-8.
https://www.ahajournals.org/doi/full/10.1161/STROKEAHA.112.650523
http://www.ncbi.nlm.nih.gov/pubmed/22474059?tool=bestpractice.com
Recombinant coagulation factor Xa (andexanet alfa)
A recombinant modified human factor Xa decoy protein that binds factor Xa inhibitors, resulting in decreased anti-Xa activity and thrombin generation. In the UK, andexanet alfa is recommended only in research for reversing anticoagulation from apixaban or rivaroxaban in adults with life-threatening or uncontrolled intracranial haemorrhage, in the form of an ongoing randomised trial mandated by the regulator.[108]National Institute for Health and Care Excellence. Andexanet alfa for reversing anticoagulation from apixaban or rivaroxaban. May 2021 [internet publication].
https://www.nice.org.uk/guidance/ta697
There is an ongoing trial, which aims to determine the efficacy and safety of andexanet alfa compared to usual care in patients presenting with acute intracranial haemorrhage within 6 hours of symptom onset and within 15 hours of taking an oral factor Xa inhibitor.[109]ClinicalTrials.gov. Trial of andexanet in ICH patients receiving an oral FXa inhibitor. Jul 2020 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03661528
Haemostatic therapy
Treatment with recombinant activated factor VII prevented haematoma growth but failed to improve clinical outcomes in a phase III trial.[21]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 May 15;358(20):2127-37.
http://www.ncbi.nlm.nih.gov/pubmed/18480205?tool=bestpractice.com
Future trials may investigate whether recombinant activated factor VII is more effective in selected patient subgroups. Additional basic research has been performed on cilostazol (a phosphodiesterase-3 inhibitor) to prevent intravenous tissue plasminogen activator-associated haemorrhagic transformation and warfarin-induced haemorrhage. Cilostazol has been shown to have protective properties on endothelial cells, vascular smooth muscle cells, and the blood-brain barrier, yet clinical trials are needed to investigate if such properties would be of benefit in haemorrhagic stroke or prevention of haematoma expansion.[110]Takagi T, Hara HJ. Protective effects of cilostazol against hemorrhagic stroke: current and future perspectives. Pharmacol Sci. 2016 Jul;131(3):155-61.
http://www.ncbi.nlm.nih.gov/pubmed/27381422?tool=bestpractice.com
[111]Kim SM, Jung JM, Kim BJ, et al. Cilostazol mono and combination treatments in ischemic stroke: an updated systematic review and meta-Analysis. Stroke. 2019 Dec;50(12):3503-11.
https://www.ahajournals.org/doi/10.1161/STROKEAHA.119.026655?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/31607242?tool=bestpractice.com
[112]McHutchison C, Blair GW, Appleton JP, et al. Cilostazol for secondary prevention of stroke and cognitive decline: systematic review and meta-analysis. Stroke. 2020 Aug;51(8):2374-85.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382534
http://www.ncbi.nlm.nih.gov/pubmed/32646330?tool=bestpractice.com