Delayed cerebral

ischemia post
subarachnoid
hemorrhage

Marcelo Lannes MD MA MSC

FRCPC
Mcgill University Health
Center
2013
 Timing
Symptoms
DCI

Exclusion of other
causes
 Confirmatory testing is often necessary
particularly in comatose patients

A = Cerebral blood flow

B = Cerebral blood volume
C = Mean transit time (MTT)
Pathophysiology Epidemiology

Therapy
Inflammation and Cerebral Vasospasm After Subarachnoid Hemorrhage
Gustavo Pradilla
Neurosurgery Clinics of North America 2010
 Subarachnoid
hemorrhage

Transient Subarachnoid
global ischemia blood

Inflammation/
Cortical Vasospasm Microthrombi
oxydative stress
spreading
ischemia

Focal cerebral
infarctions Global cerebral
atrophy
R. Loch Macdonald in
Cerebral Vasospasm, 2013
Poor outcome Springer Verlag
Sabri M, Ai J, Locovic K, MacDonald
RL Acta Neurochirurgica Supp, vol
115,pp 185-192, 2013
 Mortality
50

40

30
%

20 42

10 18

0
No vasospasm Vasospasm
 Mortality and Morbidity
50

40

30
Mortality
23
%

Severe disability 20
20

10

0
reserpine

Flamm et al:
Reversal of focal aminophiylline and
deficits with pressors isoproterenol
(Wise et al)

1960s 1972 1976 1977

Improvement in
vasospasm symptoms
with higher BPs
 Pickard:
Kassell: 58 Largest trial
patients with nimodipine
vasospasm

1982 1983 1989 1990s

Allen: clinical trial

nimodipine Triple H era
Triple H became the standard therapy without
solid evidence from proper clinical trials
Hypervolemia
Triple H became the standard therapy without solid
evidence from proper clinical trials

Incidence of ischemia
Triple H became the standard therapy without
solid evidence from proper clinical trials
Complications
There is increasing evidence against the use of
hemodilution
Effects of isovolemic hemodilution
70
58.56
60 52.25
ml/100g/min

50
40 Global Cerebral
30 Blood Flow
20 Global Cerebral O2
10 7.94 6.98 Delivery
0
Before After
hemodilution hemodilution

Ekelund et al. Acta Neurochir, 144 (2002),

pp. 703712
There is increasing evidence agaisnt the use of
hemodilution
Effects of hypervolemic hemodilution
70
58.6
60
51.4
ml/100g/min

50
40 Global Cerebral
30 Blood Flow
20 Global Cerebral O2
10 6.98 6.77 Delivery
0
Before After
hemodilution hemodilution

Ekelund et al. Acta Neurochir, 144 (2002),

pp. 703712
Hypertension seems to increase CBF,
but effects are inconsistent
Figure 3 Internal carotid artery (ICA) inlet pressure versus percentage reduction in middle cerebral artery (MCA) diameter. Hct,
hematocrit.

Joe Sam Robinson , M. Sami Walid , Sinjae Hyun , Robert O'Connell , Chris Menard , Brandi Bohleber

Computational Modeling of HHH Therapy and Impact of Blood Pressure and Hematocrit
World Neurosurgery Volume 74, Issues 23 2010 294 - 296
Statins: conflicting evidence

Magnesium: no impact on outcome

Other calcium channel blockers: no effect

Clazosentan: no effect (2 phase III trials)

Tirilazad: no effect

Cisternal thrombolysis: maybe

Prophylactic angiosplasty:
Recommendations:
Now it is called Augmentation Therapy
Euvolemia

Titrated hypertensive therapy

Cardiac output augmentation (maybe)

Endovascular therapy as rescue

 Animal studies: Khajavi:
Identification Aminophylline, Milrinone in animal
of multiple papaverine, ascorbic model of vasospasm
PDEs in brain acid
tissue

1971 1970s 1997

PDE type IV
predominates in
cerebral vessels
 Fraticelli:
Lannes:
Prospective
Case series 88 patients;
series 22
milrinone-based
patients
protocol

2001 2008 2009 2012 ?

Romero: Intra-arterial
Arakawa: 1st use in
milrinone as rescue
humans with vasospasm
therapy
7 patients
Milrinone acts at different pathways thought to be
involved in the pathophysiology of vasospasm

Milrinone

Decreased
release
Vasodilation of neutrophil
elastase

Reduced Reduced
platelet Reduced apoptotic
aggregation markers of signaling
inflammation

NFL-0387-2DC-5N
Cilostazol

Sildenafil
 MAP90

Milrinone SAH Nimodipine

Hypervol
emia
WFNS score I 12/22 patients (55%)

Use of norepinephrine 4 patients

Deaths 2 ( 9%)

Minimal disability 18 patients (82%)

2 patients lost to follow-up

 T control

Glucose
SAH Nimodipine
control

Euvolemia
 T control
Milrinone

Glucose
DCI Nimodipine
control

Euvolemia
Hunt and Hess grade I-III 66 (75%)

Use of norepinephrine 60 (68%)

Mean duration of therapy 9.8 days

Deaths 5 (5.7%)

Good outcome 66 (75%)

The way we do it at the MNH:

MAP at baseline

0.75 mcg/kg/min

Milrinone
0.1-0.2mg/kg

Triggers
No other
causes
The way we do it at the MNH:

Norepi
MAP 100
Repeat bolus

If 1.25 mcg/kg/min
& no change

Increase Q 30
min up to
2.5 mcg/kg/min

No change
after 30 min
The way we do it at the MNH:

Angioplasty

IA milrinone

Emergency
angiogram

No change
after 30 min
We should avoid repeating the same mistake