By Rajiv Advani

Chair: Carlo Cereda and Charlotte Cordonnier

D. Staykov – Perihemorrhagic edema: the hidden enemy

ICH in its acute and subacute phases, especially where a large volume is involved, is often associated with perihemorrhagic edema. Studies have shown that the volume of ICH is congruent with the volume of edema. Perihemorrhagic edema develops due to multiple pathophysiological factors; inflammation, damage to the blood-brain barrier, generation of free radicals and the toxicity of blood breakdown products. Perihemorrhagic edema can be seen up to ten days after acute ICH and is usually most pronounced during the first 7 days, this poses the question of when to evaluate edema. Potential treatments are pharmacological and involve the use of hypertonic saline, mannitol, glycerol, sorbitol, medically induced hypothermia; however all unproven at RCT level. Surgical treatment is being evaluated, where large ICH volumes are randomised to hemicraniectomy, the SWITCH trial is actively recruiting. Neuroprotective medications have been promising in animal studies and involve the use of TNF alpha inhibitors, celecoxib, deferoxamine, reactive oxygen species scavenger and can serve as potential future therapies.

N. Sprigg – Hematoma expansion and medical therapies

Hematoma expansion leads to greater risk of death and poorer outcomes for survivors at 3 months. Large ICH volumes (>30ml) tend to enlarge further. Several radiological signs can identify those at risk of hematoma expansion, but none have proven to definitively predict expansion. Non contrast CT signs include the black hole sign, the blend sign, the island sign and on contrast enhanced CT; the spot sign. Anticoagulation reversal for VKA, Dabigatran reversal and Factor Xa inhibitor reversal (currently only in clinical trials in some countries), should be actively used. Trying to administer medication rapidly by keeping the drug in the admissions unit and having point of care devices for INR can improve treatment times. Tranexamic acid (TICH2, STOP-AUST, TRIAGE) was shown to be safe, but showed no significant benefit was seen at 3 month follow up. The PATCH study showed that platelets and FFP are not indicated where surgery is not planned. Desmopressin can serve a surrogate for reversal but hasn’t yet been proven. Recombinant factor VIIa (rFVIIa) for ICH is currently being tested in the FASTEST study. Goal directed bundles seem to show the most promise; addressing fever and hyperglycemia as well as anticoagulation reversal and blood pressure management.

K. Klijn – Surgical approaches for ICH

In some parts of the world less than 5% undergo surgery for an ICH, but in other countries almost 40% have surgery. In many Chinese RCTs, medical management isn’t tested as a control arm, where minimally invasive methods are compared to hemicraiectomy. All the RCTs for ICH surgery (STICH, STICH II and MISTIE to name a few) have all been neutral. Surgery in the afore mentioned trials was performed between 28 and 58 hours (median) after admission; early surgery has therefore not been tested. Hematoma expansion is seen commonly seen and therefore challenges the rationale of not performing surgery early. The MISTIE trial showed that a 10% greater chance of improved outcome was seen for each 1ml of ICH that was removed; volume of ICH removed is a key issue. The surgical technique is important to bear in mind: hemicraniectomy has been traditionally used (STICH), however minimally invasive techniques including stereotactic aspiration, mini-craniectomy and endoscopy guided approaches can be used with or without rTPA. DIST (pilot study in the Netherlands), showed that minimally invasive surgery in smaller ICH volumes was safe (10% mortality within 10 days) and served to reduce hematoma volume/expansion. Based on these results the DIST RCT will start randomising patients shortly. Other ongoing trials include MIND, ENRICH, MISICH and EVACUTE.

C. Anderson – Blood pressure management

The current evidence on blood pressure (BP) management in acute ICH are based on a few RCTs. ATACH II and INTERACT2 trials showed neutral and borderline positive respectively. The BASC systematic review showed that all trials, when assessed in a meta-analysis, showed a neutral result for blood pressure reduction. The subgroups in the meta-analysis showed that a goal driven blood pressure reduction, with titration of the BP reducing agent, did lead to a reduction in hematoma expansion. A significant drop in BP can be harmful and therefore titration and continuous monitoring is crucial; adverse outcomes including neurological deterioration and death were seen in large drops in BP. The PATICH trial, used perioperative medical management as per INTERACT2 in addition to minimally invasive surgery showing similar outcomes. INTERACT3, is a stepped wedge trial introducing a bundle of care (SBP < 140mmHg within 1 hour, temperature reduction to < 37.5 degrees Celsius within 1 hour, INR < 1.5 within 1 hour, aggressive management of glycemia) and aims to include 8500 patients and will be closed out this year. INTERACT4 is also ongoing, and results will shed light on the use of nitrates in the prehospital setting.