1. Cedars-Sinai Medical Center and University of California Irvine
Management of Aneurysmal Subarachnoid Hemorrhage at High Volume Centers: Outcome and Beyond
Wengui Yu, MD, PhD
Cedars-Sinai Medical Center and University of California Irvine

2. Objectives Disclosure
Review current management of aneurysmal subarachnoid hemorrhage (aSAH)
Discuss the outcome of patients with aSAH at high volume hospitals and Comprehensive Stroke Center
Disclosure
Nothing to disclose

3. Subarachnoid Hemorrhage (SAH)
A neurological emergency
5-10% of all strokes
30,000-55,000 cases/yr in the U.S.
Highest morbidity and mortality among stroke types
Rupture of cerebral aneurysm is the most common etiology of spontaneous SAH

4. AHA/ASA Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage - Stroke 2012; 43:
Level of Evidence
Recommendations A
1. Treatment of high blood pressure with antihypertensive medication
2. Oral nimodipine should be administered to improve neurological outcome B
1. Hypertension should be treated, and such treatment may reduce the risk of aSAH
2. Tobacco use and alcohol misuse should be avoided to reduce the risk of aSAH.
3. After aneurysm repair, imaging study is recommended to identify remnants or recurrence of the aneurysm
4. Initial clinical severity should be determined by use of simple validated scales (eg, Hunt and Hess, WFNS)
5. The risk of early rebleeding is high. Therefore, urgent treatment is recommended.
6. aSAH is frequently misdiagnosed. A high level of suspicion should exist in pts with acute onset of severe HA.
7. Diagnostic workup should include non-con head CT. If non-diagnostic, lumbar puncture.
8. DSA is indicated for detection of aneurysm except when it was shown by a noninvasive angiogram
9. Between the time of symptom onset and aneurysm obliteration, blood pressure should be controlled.
10. Surgical clipping or endovascular coiling of the ruptured aneurysm should be performed as early as feasible
14. Low-volume hospitals (eg, <10 cases per year) should consider early transfer of patients to high-volume centers (eg, >35 cases per year) with experienced cerebrovascular surgeons, endovascular specialists, and multidisciplinary neuro-intensive care services.
Class I Recommendations

5. Management of aSAH
1. Treatment of high blood pressure (Class I; Level of Evidence A).
to prevent ischemic stroke, intracerebral hemorrhage, and cardiac, renal, and other end-organ injury.
reduce the risk of aSAH
BP be controlled to balance the risk of stroke, HTN-related rebleeding, and maintenance of cerebral perfusion pressure.
SBP <160 is reasonable (Class IIa; Level of Evidence C).

6. 2. Oral Nimodipine (Class I; Level of Evidence A)
60 mg q4h x 21 days
Improve outcomes
No effects on vasospasm
Hold if hypotension (SBP <100) or arrhythmia
Nicardipine decreases vasospasm without outcome benefit

7. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. Pickard et al. BMJ 1989:298:
Table. Demographic data and results of patients treated with nimodipine or placebo
Patients taking nimodipine
N=278
Patients taking placebo
N=276
Mean (SD) age (years)
46 (13)
48 (12)
Grade 1-3 SAH
252
243
Time from ictus to angiography (days)
5.5
5.1
Operations No
165 (59.5%)
154 (55.8%)
Time from ictus to operation (days/ranges)
10.8 (2-60)
11.3 (2-116)
Rebleeding
25 (9%)
38 (14%)
Spasm
54 (19.4%)
46 (16.7%)
Cerebral infarct
61 (21.9%)
92 (33.3%)
Death
43 (15.5%)
60 (21.8%)
Good recovery (3 month)
199 (71.6%)
169 (61.2%)

8. Calcium antagonists for aSAH Dorhout Mees et al
Calcium antagonists for aSAH Dorhout Mees et al. Cochrane Database Syst Rev. 2007: CD00277
Nine trials (2589 pts) evaluated the effect of nimodipine on functional outcome of SAH.
The relative risk (RR) for poor outcome (death or dependency) was 0.81 (95% confidence interval (CI) 0.72 to 0.92).
The absolute risk reduction was 5.3%. The corresponding number of pts needed to treat (NNT) to prevent a single poor outcome event was 19 (95% CI 1 to 51).
The results for 'poor outcome' depend largely on a single large trial of oral nimodipine. (Pickard JD 1989)

9. 3. Treatment of Ruptured Aneurysm to Prevent Rebleed Class I; Level of Evidence B).
Treatment of ruptured aneurysm should be performed as early as feasible to reduce the rate of rebleed
Complete obliteration of the aneurysm is recommended whenever possible.
For aneurysms judged to be technically amenable to both coiling and clipping, endovascular coiling should be considered.
Surgical clipping
Large aneurysms or aneurysms with broad neck.
Lower risk of re-bleed.
Endovascular coiling
Less invasive but slight higher recurrence.
Better functional recovery.

10. 3. Treatment of Major Complications
1. Hydrocephalus/Elevated ICP/Cerebral edema
External ventricular drain (EVD) or lumbar drain.
Osmotherapy with mannitol or hypertonic saline
Sedatives/paralytic agents
VP-shunt
2. Vasospasm and Delayed Cerebral Ischemia (DCI)
Maintenance of euvolemia and normal circulating blood volume is recommended to prevent DCI.
Induction of hypertension is recommended for patients with DCI.
Intra-arterial vasodilator
Balloon angioplasty

11. Hospital Case Volumes and Mortality of aSAH Johnston SC et al
Hospital Case Volumes and Mortality of aSAH Johnston SC et al. Stroke 2000;31: Cross DT 3rd et al. JNS 2003;99(5):
Multivariate-adjusted ORs for in-hospital death from SAH in hospitals with various case volumes.
Patients treated at high volume centers (>35 cases/yr) had significantly lower mortality rates (27-32% vs 39-49%).
Surgical expertise and neurointensive care improve outcome.

12. Hospital Case Volumes and Mortality of aSAH:
Data from AHA Get-With Guidelines Stroke Registry
Prabhakaran et al. Neurosurgery 2014, 75(5):
FIGURE 2 . A, plot of annual hospital SAH volume and in-hospital mortality. each point represents a hospital with the annual case volume on the x axis and hospital mortality on the y axis. B, relationship between annual hospital SAH volume (continuous variable) and in-hospital mortality with 95% confidence bands.
Among 31,973 patients with SAH from 685 hospitals, the median annual case volume per hospital was 8.5 patients. Mean in-hospital mortality was 25.7%, but was lower with increasing annual SAH volume: 29.5% in quartile 1 (range, 4-6.6), 27.0% in quartile 2 (range, ), 24.1% in quartile 3 (range, ), and 22.1% in quartile 4 (range, ). 
Previous studies using administrative databases have suggested that care at higher-volume centers may be associated with better outcomes after SAH.8-13 Based on these data and consensus opinion, The Joint Commission has adopted a threshold of 20 annual cases of SAH among several requirements for CSC designation.14 Lee Schwamm’s group at MGH investigated whether hospital SAH volume in the Get With The Guidelines (GWTG)-Stroke registry was associated with in-hospital mortality and discharge outcomes.
The registry is a large contemporary national quality improvement program in the United States. The data was from between April 2003 and April The final study cohort included 31,973 patients directly admitted to 685 hospitals.

13. SAH and Comprehensive Stroke Center Certification
The Joint Commission (TJC) launched Comprehensive Stroke Center (CSC) certification in
The goal is to improve the quality of care for patients with severe stroke
A minimal 20 annual cases of aSAH are required as a certification requirement.

14. Outcome of Patients with aSAH at a Comprehensive Stroke Center: Cedars-Sinai Medical Center (CSMC) Experience
Cedars-Sinai Medical Center in Los Angeles is one of the first 5 certified Comprehensive Stroke Center in the United States
We admitted 118 pts with aSAH between April 1, 2012 and May 30, as a Comprehensive Stroke Center.

15. Table 1. Demographics and Severities of Patients with aSAH
Variable
N = 118
Percentage
Mean  SD age (yrs)
56.3 15.0
Female sex 84
71.2%
GCS
13-15 70
59.3%
9-12 12
10.2%
3-8 36
30.5%
Hunt & Hess grade
1-3 74
62.7%
4-5 44
37.3%
Fisher grade 4

16. Table 2. Outcome of Patients with aSAH at CSMC
Discharge mRS
 # of patients  %
1-3 58
49.2%
4-5 41
34.7% 6 19
16.1%
The mortality at hospital discharge at our Comprehensive Stroke Center (16.1%) lower than that (22.1%) of the GWTG high volume hospitals (quartile 4 with cases/year). 

17. TABLE 2. Severities and Outcomes of Patients Treated with Clipping vs Coiling
Variable
Clipping (n=52)
Coiling (n=60)
p Value
Hunt & Hess grade
1-3
38 (73.1%)
38 (63.3%)
0.63
4-5
14 (26.9%)
22 (36.7%)
0.43
Fisher grade
21 (40.4%)
24 (40.0%)
0.97 4
31 (60.6%)
36 (60.0%)
0.98
mRS at discharge
4-6
22 (42.3%)
31 (51.7%)
0.55
30 (57.7%)
29 (48.3%)
0.58

18. TABLE 3. Outcome of Patients with Poor Grade aSAH at Hospital Discharge
HH Grade
# of pts
mRS 6
mRS 4-5
mRS 0-3 4 18 2 10 6 5 26 12
4 & 5 44
14 (31.8%)
22 (50.0%)
8 (18.2%)

19. SUMMARIES
BP control and oral nimodipine are proven therapy for patients with aSAH
Ruptured aneurysm should be treated with endovascular coiling or surgical clipping as early as possible to reduce risk of rebleed.
High volume hospitals have lower in-hospital mortality than low volume centers (22.1% vs 29.5%).
The in-hospital mortality at our Comprehensive Stroke Center is lower than that of the GWTG high volume hospitals (16.1% vs 22.1%).
Low-volume hospitals (<10 cases/yr) should transfer patients with aSAH to Comprehensive Stroke Center or high-volume hospitals.