Delayed cerebral ischemia, hypertension, and SAH. Should we? - ICU Revisited
26/02/19 13)48
Delayed cerebral ischemia, hypertension,
and SAH. Should we?
IIndu
nd u ced Hyper te
tensi
nsi on
o n for De
D ell ayed Ce
C erree bbrraa l I sch emia A f ter
A n eu
e ury
r y sm
smaall SSubarachno
ubar achno iid
d He m or r ha g ee.. A Ra n ddom
om ized
iz ed C lin
linical
ica l
Tr ia
i all (H
(HIM
IMA
ALA
LAIIA
A)) , by Ce
Celline
in e Ga
G atthie
hie r et a l . [[1
1]]
Now, imagine yourself in a cold room during the year of 1976. While you
smoke your cigarette, you carefully look at a 50y/o woman with
subarachnoid hemorrhage (SAH). Back then, Fisher hadn’t “invented” his
scale yet (it would be born four years later), however, Hunt and his pal Hess
wrote something that someday would become the Hunt & Hess scale. This
same Hunt, our smoker in the room (well, I’m not sure if he was a smoker,
but I think it adds some drama to the plot), thought it would be an
interesting idea to give some colloids and norepinephrine to patients with
SAH who got “obtunded with only semi-purposeful movements in response
to pain” 4-5 days after the event. Do you know if you microwave a colloid
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Delayed cerebral ischemia, hypertension, and SAH. Should we? - ICU Revisited
26/02/19 13)48
bag it becomes a corn cake? Science fact!
And that’s how our saga begins: with a guy inducing hypertension in 7
dudes with SAH. Sounds crazy, right? Yeah, it gets better! More than 50
years late, after ZERO good quality trials, we’re still doing it. Trying to
normalize physiology might make sense, but prophylactic antiarrhythmics
were the gold standard for MI some time ago. In fact, we have no idea what
we’re doing. Colloids, hypervolemia, hemodilution, and hypertension are a
dictionary de!nition of despair!
We don’t do hypervolemia, hemodilution, and colloids no more. At least I
hope we don’t! I mean, I don’t, do you? However, hypertension is still here!
For how long? That was the question our friends who love tulips and other
green herbs which I shall not mention tried to answer with the HIMALAIA
trial!
Does induced hypertension in patients with delayed cerebral ischemia
(DCI) improves outcomes in 3 months?
It was a multicenter, single-blinded, randomized, controlled trial which
enrolled patients from 2009-2015. Now, some de!nitions:
–D
DC
CII: Decrease of at least 1 point on the Glasgow Coma Scale or
development of new focal neurological de!cits lasting at least 1 hour,
excluding any other possible causes (bleeding, hydrocephalus, seizure,
infection…).
–In
Incclu
luss io n cri te
terrii aa: >18y/o, aneurismatic SAH, a n d DCI.
–E
Exclus
xclus io n cri
cr i te
terrii aa: untreated symptomatic aneurysm, spontaneous
MAP>120mmHg, among others.
Once randomized, the intervention should be started within 3 hours after
the start of clinical symptoms of DCI (hypertension group). In the control
group, the MAP shouldn’t be <80mmHg. The intervention consisted of
starting vasopressors asap targeting symptoms resolution or until
MAP=130mmHg or SBP=230mmHg. If the patient improved, the drug was
tapered after 48h, if didn’t in 24h, treatment was tapered.
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Delayed cerebral ischemia, hypertension, and SAH. Should we? - ICU Revisited
26/02/19 13)48
The primary outcome was a mod
m odii !ed Ra
R an
n kin
k in Scal
S cal e sco r e > 3 a t 3
m o nntthhs!
s
They expected a sample size of 240 patients to detect a relative risk of 0.6
for primary outcome with induced hypertension. Unfortunately, due to slow
recruitment and lack of e"ect on cerebral perfusion scans, the trial was
stopped early, after only 41 patients were randomized.
R
Res
e sults
ults
Patients characteristics are shown in the table below:
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Delayed cerebral ischemia, hypertension, and SAH. Should we? - ICU Revisited
26/02/19 13)48
1- Gathier CS, van den Bergh WM, van der Jagt M, et al. Induced Hypertension for
Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage Stroke. 2018;
49(1):76-83.
Small sample size sucks. Lots of unbalance. Apparently, patients in the
hypertension group were sicker. Over the !rst 24h, the MAP was 11.1mmHs
higher in the intervention group, while this di"erence disappeared after 48h
(below).
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Delayed cerebral ischemia, hypertension, and SAH. Should we? - ICU Revisited
26/02/19 13)48
1- Gathier CS, van den Bergh WM, van der Jagt M, et al. Induced Hypertension for
Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage Stroke. 2018;
49(1):76-83.
There was no di"erence in the primary outcome between groups: adjusted
risk ratio 1; 95% CI, 0.6–1.8. The ratio for serious adverse events 2.1; 95%
CI, 0.9–5.0.
Data from this study was also collected for another study [2], which
evaluated the e"ect of induced hypertension on cerebral blood #ow with
computed tomographic perfusion (CTP). The !rst exam was made the
symptoms onset, and the second after 24-36h. Change in overall CBF
(ml/100g/min) was 0.1 (−31 to 43) in the hypertension group vs −8.5 (−42
to 30) in the control group (p=0.25).
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Delayed cerebral ischemia, hypertension, and SAH. Should we? - ICU Revisited
26/02/19 13)48
But what does this data show us? Although it makes a huge physiological
sense, does the bene!t is overcome by the side e"ects? Does induced
hypertension is the new hemodilution? I really don’t know. Who doesn’t
love to see patients “waking up” after some good old norepinephrine? I do
also like to live dangerously.
Most of what we do or did, like the Triple-H therapy, is aimed to increase
blood #ow, and it’s somehow based on Poiseuille law:
I do remember another trial I shall not mention which we already
discussed here (link) that also was based on a formula to improve oxygen
delivery:
And we all know how that turned out!
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Page 7 of 10
Delayed cerebral ischemia, hypertension, and SAH. Should we? - ICU Revisited
26/02/19 13)48
1- Gathier CS, van den Bergh WM, van der Jagt M, et al. Induced
Hypertension for Delayed Cerebral Ischemia After Aneurysmal
Subarachnoid Hemorrhage Stroke. 2018; 49(1):76-83.
2- Gathier CS, Dankbaar JW, van der Jagt M, et al. E"ects of Induced
Hypertension on Cerebral Perfusion in Delayed Cerebral Ischemia After
Aneurysmal Subarachnoid Hemorrhage Stroke. 2015; 46(11):3277-3281.
P
Ph
h ot
o to
o C redi t
–dispatcheseurope
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