1	Endovascular and ICU Management of Ruptured Cerebral Aneurysms Brian L. Hoh, M.D. Assistant Professor of Neurosurgery and Radiology University of Florida College of Medicine December 18, 2006
2	Ruptured Cerebral Aneurysms Endovascular Treatment of Ruptured Cerebral Aneurysms Diagnosis Treatment Neurovascular center Anticoagulation Reason for anticoagulation Anticoagulation after EVD Heparin-induced thrombocytopenia Vasospasm Risk of stroke Detection of vasospasm Triple-H therapy Endovascular treatment Statins Magnesium
3	1. Endovascular Treatment of Ruptured Cerebral Aneurysms
4	Ruptured Cerebral Aneurysms 30,000 SAH in U.S. each year¹ Though less frequent than other stroke subtypes, SAH affects younger population and results in 30-50% mortality and 50% morbidity² Lifetime economic cost of SAH for individual $228, 030 (the highest among all stroke subtypes)³ Aggregate costs of SAH in U.S. for one year $5.6 billion³ Estimated 3.6-6.0% of population has an intracranial aneurysm^4,5
5	Endovascular Treatment of Ruptured Cerebral Aneurysms A. Diagnosis
6	Diagnosis of Ruptured Cerebral Aneurysms Cerebral angiography gold standard diagnostic modality for ruptured cerebral aneurysms CT angiography Non-invasive Performed quickly Lower risk of morbidity Requires less resources More suitable for unstable pts 223 patients prospective CTA found 100% of ruptured or symptomatic aneurysms
7	Endovascular Treatment of Ruptured Cerebral Aneurysms B. Treatment
8	Treatment of Ruptured Cerebral Aneurysms Craniotomy and microsurgical clipping Endovascular coiling
9	Cerebral Aneurysm Coiling
10	Cerebral Aneurysm Coiling
11	ISAT STUDY International Subarachnoid Aneurysm Trial⁸ 2143 SAH patients randomized to clipping or coiling
12	Complex and Wide-neck Aneurysms
13	Stent-Assisted Coiling
14	Complex Aneurysms
15	Endovascular Treatment of Ruptured Cerebral Aneurysms C. Neurovascular Center
16	"Important to have multidisciplinary team" Important to have multidisciplinary team Patient outcome affected by: Hunt Hess grade, Fisher Score, Age, Aneurysm size
17	High Volume Center for Aneurysms 350-400 aneurysms treated at Shands 200-250 aneurysms coiled
18	Multidisciplinary Treatment of Aneurysms 56 year old woman with Hunt Hess 1, Fisher 3 SAH from ruptured Acom aneurysm Attempted coiling at another hospital c/b aneurysm perforation
19	2. Anticoagulation
20	2. Anticoagulation A. Reason for anticoagulation
21	Anticoagulation for Aneurysm Coiling Clinically symptomatic thromboembolic complications occur in 2.4% of aneurysm coilings¹⁰ MRI-detected thromboemboli found in 61%¹¹ Heparinization standard protocol^10,12 Started during procedure For 24 hours afterwards Antiplatelet agent
22	2. Anticoagulation B. Anticoagulation after EVD
23	Anticoagulation after EVD Placement SAH pts often require EVD Safe to heparinize for coiling soon after EVD? 119 pts with EVD+heparin for coiling compared to 251 pts with EVD+no heparin
24	Anticoagulation after EVD Placement
25	2. Anticoagulation C. Heparin-induced thrombocytopenia
26	Heparin Induced Thrombocytopenia in SAH 389 SAH patients; 15% had HIT II Diagnosis: Plt <100K or <50% baseline 4-14 days after heparin exposure Exclusion of other causes of thrombocytopenia Resolution of thrombocytopenia after heparin cessation
27	Heparin Induced Thrombocytopenia in SAH HIT II: 22 pts with thrombotic complications (37%) compared to 7% of non-HIT pts 39 pts with new hypodensities on CT (66%) compared to 40% of non-HIT pts 29% mortality compared to 12% mortality in non-HIT pts
28	Heparin Induced Thrombocytopenia in SAH
29	3. Vasospasm
30	Vasospasm Vasospasm in SAH Vasospasm single leading cause of morbidity and mortality after aneurysmal SAH¹⁶ Angiographic in 70%, clinical in 30%¹⁷ Despite maximal medical therapy, 50% of pts with clinical vasospasm will develop stroke¹⁸
31	3. Vasospasm A. Risk of stroke
32	Vasospasm Causes Stroke All CT scans of 619 consecutive aSAH pts reviewed for new hypodensities New hypodensities found in 189 pts (30%) Etiology for hypodensities determined
33	Vasospasm Causes Stroke
34	Effect of Surgery or Coiling on Vasospasm Debate regarding effect of aneurysm surgery versus coiling on vasospasm Case series showing less vasospasm with coiling^20-23 Others believe surgery beneficial because blood can be washed out
35	Effect of Surgery or Coiling on Vasospasm Factors predictive of symptomatic vasospasm Amount of blood on CT (Fisher Grade) Clinical condition of patient (Hunt Hess Grade) Not surgery versus coiling
36	3. Vasospasm B. Detection of vasospasm
37	Detection of Vasospasm Detection of Vasospasm Invasive Cerebral angiography (gold standard) Non-invasive Clinical neurologic exam Transcranial Doppler CT angiography/perfusion
38	Transcranial Doppler Transcranial Doppler Non-invasive Bed-side test No contrast load Can be performed multiple times a day Meta-analysis²⁴ TCDs best for MCA Highly specific (99%) High PPV (97%) Sensitivity (67%)
39	CT Angiography/Perfusion 23 patients who underwent both CTA/CTP and catheter angiography 19 clinically symptomatic vasospasm 4 angiographic vasospasm Blinded neuroradiologist read CT perfusion maps CTP Sensitivity 84% Specificity 100% PPV 100%
40	3. Vasospasm C. Triple-H Therapy
41	Triple-H Therapy Triple-H Therapy (Hypertension, Hypervolemia, Hemodilution) Described and studied in 1980s^26-27 Found in case series to reverse delayed ischemic neurologic deficits in aneurysmal SAH patients Thought to promote pial collateral flow to ischemic areas
42	Prophylactic Triple-H Therapy Prophylactic Triple-H therapy not effective^28-30 Triple-H therapy reverses DIND in case series Prophylactic triple-H therapy studied extensively Prophylactic triple-H therapy does not prevent vasospasm Associated with higher complications (pulmonary, cardiac)^29-30 Proven not effective in randomized controlled trials^28-29 Proven not effective in meta-analysis³⁰
43	Triple-H Therapy and Multiple Aneurysms 40 pts with 124 aneurysms 51 treated (37 clipped, 14 coiled) 73 untreated Aneurysm size Range 2-20mm Mean 4.5mm ³ 10mm: 5 (6.8%) Triple-H therapy started on mean SAH-day 6.7 Mean duration of triple-H therapy 7.3 days 28 aneurysms eventually treated at later procedures (25 clipped, 3 coiled); mean interval to treatment 6.9 months
44	3. Vasospasm D. Endovascular treatment
45	Endovascular Treatment of Vasospasm 530 pts treated with PTBA 62% improved clinically 5.0% major complications 1.1% vessel rupture 24 pts treated with IA nicardipine 42% improved clinically 4% complications IA papavarine no longer used (increased ICP, seizures, neurotoxic)
46	3. Vasospasm E. Statins
47	Statins and Vasospasm 80 aSAH pts randomized to 40mg pravastatin or placebo Vasospasm 42.5% vs 62.5% (P<0.01) Severe Vasospasm 17.5% vs 30% (P<0.05) DINDs 5.0% vs 30% (P<0.001) Mortality 5.0% vs 20% (P<0.05)
48	Statins and Vasospasm 39 aSAH pts randomized to 80mg simvastatin or placebo Significant reduction in vasospasm in simvastatin group Vasospasm 26% vs 60% (P<0.05)
49	3. Vasospasm F. Magnesium
50	Magnesium and Vasospasm 283 aSAH pts randomized to MgSO4 64mmol/L per day vs placebo MgSO4 Risk reduction for delayed cerebral ischemia 34% Risk reduction for poor outcome 23% Relative risk for excellent outcome 3.4
51	Magnesium and Vasospasm 38 aSAH pts given 12gm MgSO4 IV infusion qD for 12 days Compared to matched controls Significantly lower symptomatic vasospasm: 18% vs 42% (P<0.05) Trend towards better mRankin Scale outcome (P=0.084)
52	Conclusions Despite advancements in aneurysm treatment (endovascular) and ICU management of SAH, morbidity and mortality is still signficant Challenge to find novel therapies to improve our treatment of these sick patients Exciting time at U.F. in treatment of SAH patients Neuro ICU Imaging Novel therapies