Subarachnoid Hemorrhage presentation.pdf

Clinical pharmacy

1. Subarachnoid Hemorrhage
Management Overview
Presented By
Mohamed Rawy
Clinical Pharmacist , BSc, BCPS, BCCCP

2. Talk outline:
-Definition
-Pathophysiology
-Clinical manifestations
-Diagnosis
-Management
-Monitoring

3. Case …
-A 45 Y old women develops sudden onset of headache characterized
by R sided and worst headache in her life while she was at work
typing up a manuscript
-While in the ED She starts to become lethargic & require frequent
stimulation to arouse
-CT Brain was done and shows diffuse SAH & Hydrocephalus
-EVD was placed and patient mental status is improved
-She did aneurysmal coiling on day of admission
-On day 7 she developed new agitation & LL weakness

4. Definition …
-It is a rare, life-threatening type of stroke that occurs when a blood vessel
in the brain ruptures and bleeds into the space between the brain and the
arachnoid membrane
-Represents 3% of proportion of stroke
docIcon
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5. Hemorrhagic
Stroke
Intracerebral Hemorrhage Subarachnoid Hemorrhage

6. Part 2B
Subarachnoid Hemorrhage
(SAH)

7. Definition …
-Subarachnoid hemorrhages:
•Second type of hemorrhagic stroke
•Most often caused by:
1.Aneurysm
2.Trauma
3.Perimesencephalic non-aneurysmal subarachnoid hemorrhage
4.Intracranial arterial dissection
5.Cerebral Venous Thrombosis (CVT)
6.Cerebral Amyloid Angiopathy (CAA)
7.Vascular malformations
8.Brain tumors
9.Moyamoya disease
10.Bleeding disorders (Ex. DIC , Hemophilia)
11.Illicit drug use

8. Subarachnoid
Hemorrhage
Spontaneous
5-10%
Traumatic
40-60%

9. Clinical Manifestations …
-Sudden & Severe Headache (Worst headache ever)**
-Vomiting
-Decreased conscious level
-Fever
-Visual disturbances
-Numbness , Neck stiffness
-Seizure

10. Diagnosis …
- CT Brain without contrast
- Lumbar Puncture if CT fails to show
blood … Xanthocromia
- CT Angiography (CTA) or Magnetic
Resonance Angiography (MRA) or Digital
Subtraction Angiography (DSA)
DSA is the gold standard for cerebral vessel imaging
- CBC , Coagulation profile , ECG , Cardiac
Troponins , ECHO

11. Diagnosis …
-Ottawa SAH Rule

12. Diagnosis …
-Grading severity of SAH
•Hunt & Hess grading system (hemorrhage severity)
•Fisher Scale (vasospasm risk)
•VASOGRADE (delayed cerebral ischemia prediction)
•World Federation of Neurological Surgeons (WFNS) grading scale
There is no universally accepted grading scale for SAH, but the scales
presented are among the most commonly used and have some value in
predicting the neurological outcome (probability of death and
expected level of disability)

13. Pathophysiology …
- Aneurysm rupture causing bleeding
- Elevated ICP
- Hydrocephalus
- Vasospasm

14. Treatment …
Primary measures should be
initiated urgently in the ED
The goal is to stabilize the
patient and prevent early re-
bleeding and secondary brain
injury

15. Treatment …
•Initial symptomatic management:
-Blood Pressure control
-Reversal of antithrombotics or anticoagulants
-Maintain Eu-volemia
-Nimodipine
-VTE prophylaxis
-Seizure Prophylaxis
-Pain control
-Surgical repair of aneurysm

16. Initial symptomatic
management of SAH

17. Treatment …
Blood Pressure Control
-When blood pressure control is necessary, short acting intravenous
Labetalol, Nicardipine, Clevidipine, or Enalapril are preferred
-Use of vasodilators such as nitroprusside or nitroglycerin should be
avoided (Increase cerebral blood volume and thus increase ICP)
-There is no specific target BP according to AHA guidelines
-Previous guidelines recommend For most patients with acute SAH,
use a target SBP <160 mmHg or MAP <110 mmHg

18. Treatment …
Blood Pressure Control
-Start IV antihypertensive if high BP (i.e. SBP >180 or DBP >120 mmHg)
-The specific target should be individualized based on severity of initial
blood pressure elevation, presence of brain swelling, and risk of kidney
impairment
-Always keep in mind risk of infarction if low MAP
-Avoid hypotension (MAP <65mmHg) & Keep CPP of ~70mmHg
CPP= MAP-ICP

19. Treatment …
Most common drugs
used for the treatment
of hypertensive
emergencies

20. Treatment …
Reverse Antithrombotic …
-Discontinuation of all antithrombotic agents and reversal of all
anticoagulation for acute SAH until the aneurysm is definitively
repaired by surgery or coiling, in agreement with guidelines
For more details , kindly go back for previous
lecture entitled Intracerebellar Hemorrhage ☺

21. Treatment …
Reverse Antithrombotic …
Antithrombotic Reversal strategy
Antiplatelet -Platelet transfusion only if neurosurgery is planned , Keep count > 100.000
-Single dose IV Desmopressin 0.4mcg/kg over 30 minutes (week recommendation)
Warfarin -PCC (dose according to INR) , If unavailable then use FFP (10-15mL/kg)
-Vitamin K 10mg by slow iv infusion over 10-20 minutes
NOAC -Andexanet alfa (dosing depend on dose & last time of administration of NOAC)
-If unavailable then use PCC
Dabigatran
-Idarucizumab (5mg on 2 separate doses no more than 15 minute between them)
-If Unavailable then use PCC
-Hemodialysis is an option if all fail
Fondaparinux -PCC or andexanet alfa (limited evidence)
Heparins -Protamine sulfate (dosing depend on either UFH or LMWH , Administration by SC or IV
Infusion for UFH & Timing of last administered dose)
Argatroban
Bivalirudin
-No need for reversal (short half lives … minutes )
-rFVIIa (limited evidence)

22. Treatment …
Reverse Antithrombotic …
When to Restart Anticoagulation ???
-One size does not fit all !!
-The optimal time for resumption is less clear, but available data suggest a
window of between 7 and 14 days and 4 and 8 weeks depending on
individual bleeding and thromboembolism risk
-LAAC is a safe alternative to reduce ischemic stroke in OAC-ineligible
patients if Atrial Fibrillation
-IVC Filter is safe alternative in patients with DVT as a bridge until
Anticoagulation is initiated
-Start with short acting agents (UFH or LMWH) & delay OAC starting
-Serial CT scans should be done to monitor the stability of hematoma
-Mechanical DVT Prophylaxis can be started after 1-4 days of SAH stability

23. Treatment …
Reverse Antithrombotic …
-Role of Anti-fibrinolytic ?
•Neurocritical Care Society guideline & AHA guidelines recommend against
the administration of antifbrinolytic therapy to prevent re-bleeding of
ruptured aneurysms in patients with aSAH
•Tranexamic acid has NOT been shown to reduce the risk of poor outcomes
including death, vegetative state, or severe disability
•It is only an option if treatment to secure the aneurysm by endovascular
coiling or neurosurgical clipping is suitable but cannot be carried out
within 24 hours of hospital admission
•Short course (less than 3 days) of Tranexamic acid 1g QID IV & discontinue
after securing the aneurysm

24. Treatment …
Maintain Euvolemia …
-Avoid hypovolemia (risk factor for ischemic complications)
-Avoid Triple H therapy (Hypervolemia , Hypertension , Hemodilution)
-Keep Sodium level of 145-155 mEq/L to reduce cerebral edema

25. Treatment …
Vasospasm prevention …
Nimodipine
-Only Selective CCB has FDA approval for prevention of vasospasm & DCI
-Can be administered via PO or NGT or Intravenous Infusion
-Oral & IV doses are Not interchangeable
-Oral Dosing is 60mg every 4h for 21 days , should be started within 96h of
symptom onset & continued for 21 days
-Dose can be halved to 30mg every 2h for patients with low blood pressure
-If NPO or No Ryle then start giving IV infusion through CVL only
-Dosing is starting with 1mg/h for first 2h then increased to 2mg/h if well
tolerated for minimum of 5 days & maximum of 14 days with concurrent
administration of free flowing fluid of 40mL/h

26. Treatment …
Vasospasm prevention …
-Patients are typically monitored for the development of vasospasm daily
from Day 4 to Day 14
-The AHA/ASA 2023 guidelines recommend CTA, CT perfusion, continuous
electroencephalography (cEEG), or transcranial Doppler (TCD) as
reasonable options
-TCD is commonly performed because it can be completed at bedside, is
noninvasive, and does not require any contrast

27. Treatment …
Vasospasm prevention …
Other strategies of uncertain benefit (No difference in SAH outcome)
-Lumbar Drainage
-Clazosentan
-Statins (Simvastatin)

28. Treatment …
Seizure Prophylaxis …
-Controversial !!!
-Initiation of anti-seizure medications in higher-risk patients include
subarachnoid clot, intracerebral hemorrhage, Cortical infarction,
Hydrocephalus and aneurysm in the middle cerebral artery
-Levetiracetam is generally the preferred agent based on its safety profile
-Dosing is LD of 20mg/kg iv followed after 12h by a MD of 1g BID iv for up to
7 days (Maximum dose is 1.5g BID)
-Avoid phenytoin because of it is associated with worse neurologic and
cognitive outcome after SAH

29. Treatment …
DVT Prophylaxis …
-IPC is started on admission and prior to aneurysm treatment
-Heparin (LMW or unfractionated) can be added once the aneurysm is
secured for patients who continue to have restricted mobility “usually 24h
after securing the aneurysm”
-Continue prophylaxis till patient becomes fully ambulant

30. Treatment …
Pain Control …
-Short-acting opiates are typically used (Ex. IV Fentanyl , IV Morphine)
-Acetaminophen 500mg Q4-6h
-Avoid aspirin (NSAIDs) before aneurysm is secured (risk of bleeding)
-For more severe pain start IV or suppository Codeine or Tramadol
-Use Dexamethasone as a last line for refractory headache associated with
brain edema (limited data)
Caution with use of narcotics as it may induce
constipation which increase the strain and may
increase pressure causing aneurysmal rupture

31. Treatment …
Bed rest …
-Give stool softener to decrease pressure on aneurysm
-Start SUP using either PPI or H2 blockers
-Give antiemetic

32. Treatment …
Aneurysm Treatment …
-Aneurysm repair with surgical clipping or endovascular coiling is the
only effective treatment to prevent this occurrence and should be
performed as early as feasible, preferably within 24 hour

33. Managing early
complications of SAH

34. Treatment …
•Managing early complications:
-Re-bleeding
-Vasospasm & delayed cerebral ischemia
-Elevated intracranial pressure
-Hyponatremia
-Seizures
-Anemia
-Cardiopulmonary complications
-Prevention of VAP
-Hyperglycemia
-Fever

35. Treatment …
Re-bleeding …
-After aneurysmal SAH, the patient is at substantial risk of early re-bleeding
(4 to 14 % in the first 24 hours, with maximal risk in the first 2 to 12 hours)
-Re-rupture is associated with a high mortality (70%)
-Patients with re-bleeding should have emergency aneurysm repair

36. Treatment …
Vasospasm & Delayed Cerebral Ischemia …
-It affects approximately 30% of patients with aneurysmal SAH, typically
between 4 and 14 days after symptom onset
-Symptoms include hemiparesis, aphasia, apraxia, hemianopia, or neglect
-Most common cause is assumed to be vasospasm
-Vasospasm is believed to be produced by spasmogenic substances
generated during the lysis of subarachnoid blood
-Fisher score used to predict the likelihood of vasospasm & DCI
-If not treated early >>> Ischemic Stroke

37. Treatment …
Vasospasm & Delayed Cerebral Ischemia …
-Prevention by Nimodipine , Euvolemia , induce hypertension
-Surveillance by CTA with or without CT perfusion
-Treatment:
1.Hemodynamic augmentation
2.Balloon angioplasty
3.Intra-arterial vasodilators
4.Stellate ganglion block

38. Treatment …
Vasospasm & Delayed Cerebral Ischemia …
1. Hemodynamic augmentation
- Increase MAP to enhance cerebral perfusion either by iv fluids crystalloids or
colloids +/- Vasopressors (Norepinephrine or Phenyephrine) +/- Inotropes
(Dobutamine or Milrinone)
- Avoid Triple-H therapy
2. Balloon angioplasty
- For patients with focal vasospasm of larger cerebral arteries refractory to
hemodynamic augmentation
3. Intra-arterial vasodilators
-For patients with focal or diffuse vasospasm of smaller cerebral arteries
refractory to hemodynamic augmentation
-Intra-arterial nicardipine , milrinone , papaverine , nimodipine , verapamil
Intra-arterial vasodilators and angioplasty also may be used in combination

39. Treatment …
Vasospasm & Delayed Cerebral Ischemia …
A comparison of
selected commonly
used vasoactive agents

40. Treatment …
Vasospasm & Delayed Cerebral Ischemia …
Typical Agents for Intra-arterial Use for Cerebral Vasospasm

41. Treatment …
Elevated ICP management …
-Hydrocephalus affects 20 - 30 % of patients with SAH
-Treatment options include:
1.Osmotic therapy including either IV Mannitol or Hypertonic Saline
2.Using External Ventricular Drain (EVD) to remove excess CSF
3.Craniotomy with hematoma evacuation & CSF drainage
4.Reducing cerebral metabolism, which lowers CBF and reduces ICP:
•Hyperventilation
•Pentobarbital
•Propofol
•Neuromuscular blocker
•Hypothermia
Corticosteroids should not be administered for treatment of elevated ICP

42. Treatment …
Elevated ICP…
-EVD or lumbar drainage for patients who have a deteriorating level of
consciousness and evidence of elevated ICP and/or hydrocephalus
-EVD placement may be complicated by infection (ventriculitis/meningitis),
particularly when drainage is continued for >3 days and bleeding (eg,
hemorrhage along the catheter tract)

43. Treatment …
Elevated ICP…
-Osmotic therapy including either IV Mannitol or Hypertonic Saline
Hypertonic saline 3% - 23.4% is preferred
•3% dose: 0.1-1 mL/kg/h to achieve a target sodium level of 145-155 mEq/L
•Can be administered through CVL or PL for several hours till CVL is obtained
•23.4% is given as an intermittent boluses instead of continuous infusion
•It does not cause hypovolemia or volume depletion like mannitol
•S.E. include Pulmonary edema & may cause NAG metabolic acidosis
Mannitol 20% is an alternative to HTS
•Boluses of 0.25 - 1 g/kg every 4-6 hours as needed using CVL Only
•Check Sodium level Every 4-6h , Kidney function tests & serum osmolarity
•S.E include Hypovolemia , AKI & Hypokalemia
•A serious albeit theoretical concern with mannitol use is leakage into brain tissue
in patients with disruption of the blood-brain barrier, with consequent reversal of
the osmolar gradient and rebound cerebral edema

44. Treatment …
Hyponatremia …
-Affects about 30%of patients with SAH Either due to SIADH or CSWS
How to differentiate between SIADH & CSWS ??
CSWSSIADH
Increased DecreasedUrine Volume
DecreasedNormal or ExpandedECF Volume
Yes NoHemodynamic Instability with Fluid Restriction
LowLowSerum Sodium
Low LowSerum Osmolality
Increased Increased Urine Sodium
IncreasedIncreasedUrine Osmolality

45. Treatment …
Hyponatremia …
How to differentiate between SIADH & CSWS ??
The two disorders have similar manifestations, and it is only the
presence of clear evidence of volume depletion (eg, hypotension,
decreased skin turgor, possibly increased bloodureanitrogen/serum
creatinine ratio) despite a urine sodium concentration that is not low
that suggests that CSW might be present rather than SIADH

46. Treatment …
Hyponatremia …
-CSWSManagement:
1.Avoid Fluid Restriction
2.Volume Repletion with Normal Saline or HTS 3%
3.Salt tablets when able to tolerate oral medications (1-2g TID)
4.Fludrocortisone (0.1-0.4 mg/day)
Hypovolemic Hyponatremia

47. Treatment …
Hyponatremia …
-SIADHManagement:
1. We Recommend Avoid Fluid Restriction to 1.5L/day
2. We Recommend Oral Urea OR Oral Sodium Chloride in combination of Low
dose loop diuretics to reduce urinary concentration (i.e. Lower the urine osmolality
by increase water excretion)
3. We recommend against use of Demeclocycline
4. We recommend against use of AVP antagonists
Fluid Restriction !!!
may not be appropriate for
hyponatremia associated with
subarachnoid hemorrhage
Because these Patients are at
risk for cerebral vasospasm and
infarction which is increased by
a fall in blood pressure
Solution is:
hyponatremic patients with SAH
should be treated with
Hypertonic saline 3% to both
preserve cerebral perfusion and
prevent complications from
hyponatremia-induced brain
swelling
Euvolemic Hyponatremia

48. Treatment …
Hyponatremia …

49. Oral UreaAVP Antagonists DemeclocyclineOral NaclIV Nacl 0.9%
Induce osmotic
excretion of free H2O

(Predictable excretion of
H2O)
Inhibition of Renal V1 & V2
receptors So the Block the
action of ADH on this
receptors so prevent water
reuptake without electrolyte
disturbance (Aquaretics)
Inhibition of ADH
activity due to
inhibition of
aquaporin water
channels
Na
Supplementation
Na
Supplementation
Mechanism of
action
Euvolemic
Hypervolemic
Euvolemic
Hypervolemic
Euvolemic
Hypervolemic
Hypovolemic
Euvolemic
HypovolemicIndication
15-30 g/day
up to 90g/day
Conivaptan
20mg LD
Then 20-40mg IV
for Only 4 Days due to DDI
Tolvaptan (V2 Selective)
15-60mg PO
Use is no longer than 30 days
150-300mg Q6h
Up to 1200mg/day
4-16g/d
(1g=17mEq Na)0.5-1.5 ml/kg/hDosing
Modest ,
Prompt (First 24h)
Modest ,
Prompt (First 24h)
Modest ,
Delayed (1w)
Modest ,
Moderate (2d)
Modest , Moderate
(2d)Efficacy
Vomiting
Diarrhea
Ensure absence of Renal
Failure Or Hepatic
Encephalopathy
Hepatic & Renal toxicity
Thirst
Higher risk of ODS
Cost
DDI
GI Upset
Hepatotoxicity
Photosensitivity
Chelation with metals
Thirst Fluid OverloadS.E
Management options for Hyponatremia

50. Treatment …
Hyponatremia …
What about treatment of SIADH with Normal Saline?
Normal saline makes hyponatremia worse in SIADH
-Assuming the patient is euvolemic, the administered sodium is excreted in the urine
because the response to aldosterone and atrial natriuretic peptide is normal , However
the water is retained because of the persistent action of ADH.
- In SIADH, sodium handling is intact and only water handling is out of balance from too
much ADH.
-Therefore when administering 1 liter of normal saline to a patient with SIADH and a
high urine osmolality, all of the sodium will be excreted, but about half of the water
will be retained – worsening the hyponatremia , This is because the concentration of
sodium in the urine of a patient with SIADH is going to be higher than the
concentration of sodium in normal saline.

51. Treatment …
Seizures …
-Acute seizures occur in 8-15 % of patients with SAH
-Risk factors include subarachnoid clot, intracerebral hemorrhage, Cortical
infarction, Hydrocephalus and aneurysm in the middle cerebral artery
-Seizures that occur prior to aneurysm treatment are often a sign of early
re-bleeding
-Non convulsive status epilepticus (NCSE) and subclinical seizures are
increasingly recognized as a potential contributor to prolonged impairment
of consciousness in patients after SAH , Diagnosis of NCSE and subclinical
seizures requires a high index of suspicion as patients with NCSE are often
those with poor neurologic grade and other neurologic complications of
SAH, making it difficult to detect subclinical seizures; continuous EEG
monitoring is often required

52. Treatment …
Seizures …
-Patients with acute seizures after SAH are treated with antiseizure
medications to prevent recurrence
-Agents with favorable side effect profile, such as levetiracetam are used
-Avoid phenytoin because its use has been associated with worse cognitive
outcomes in patients with aneurysmal SAH
-For most patients with SAH and acute seizures, we typically start weaning
antiseizure medication after one week, unless seizures recur
-While acute seizures are a risk factor for developing epilepsy, a longer
duration of treatment does not reduce the risk of epilepsy, and most
patients do not require long-term antiseizure medications

53. Treatment …
Anemia …
-Occurring in 18 % of patients during their hospital stay in one report
-Use a conservative transfusion threshold of 7 g/dL for blood transfusion
-Optimal hemoglobin level is to be 8-10 g/dL

54. Treatment …
Cardiopulmonary complications …
-Pulmonary edema and cardiac arrhythmias complicate 23-25 % of
SAH cases respectively
•Takotsubo cardiomyopathy
•ECG abnormalities
•Left ventricular dysfunction
•Troponin release

55. Treatment …
Prevention of ventilator-associated pneumonia …
-For patients with severe SAH who require initial endotracheal
intubation, we administer a single dose of intravenous (IV)
ceftriaxone 2 g to decrease the risk of ventilator-associated
pneumonia (VAP)

56. Treatment …
Prevention of Fever …
-Feverof infectious and noninfectious origin is a common complication
of SAH, particularly in those with a higher neurologic grade, and is
associated with a poor prognosis
-Body temperature should be monitored and infection should be ruled
out or treated
-Treat fever with antipyretics and cooling blankets

57. Treatment …
Prevention of Hypo/Hyperglycemia …
-Keep target BGL <180mg/dL associated with lower mortality than
target of 81-108mg/dL
-Treat BGL > 180-200mg/dL is reasonable to improve outcomes
-Treat BGL < 60mg/dL to reduce mortality

58. Treatment …
Hypothalamic-pituitary dysfunction …
-It is common after SAH, but the clinical implications and appropriate
treatment is uncertain.
-Routine administration of glucocorticoids is not recommended after
SAH but may be considered in patients who are unresponsive to
vasopressor therapy for vasospasm

59. Treatment …
Neurologic morbidity …
-Long-term complications of SAH include neurocognitive dysfunction,
epilepsy, and other focal neurologic deficits
•Cognitive impairment
•Mood and sleep disorders (Depression, anxiety, and sleep
disturbances)
•Anosmia
•Epilepsy

60. So how you can manage a patient
with
Subarachnoid Hemorrhage ??

61. -Check ABC first …
•Airway: Check patency of airway & need for ETT
•Breathing: Check need for oxygen
•Circulation: Need for IV Fluids +/- Vasopressors
-Obtain emergency CT Brain
-Obtain initial labs including CBC , Coagulation Profile , Electrolytes , Cardiac troponins ,
ECG , BGL
-Check need for surgical intervention (Ex. EVD)
-Manage hypertension (Target SBP <140-160mmHg)
-Reverse anticoagulation
-Give Tranexamic acid IV if there is a delay in aneurysmal
-Give Levetiracetam IV as a seizure prophylaxis
-Manage elevated ICP (Give HTS or Mannitol)
-Pain management for headache
-Start Nimodipine
-Start IPC as a DVT Prophylaxis
-Use IV Fluids isotonic & avoid hypotonic one , Keep serum Na >145mEq

62. References …
-2023 Guideline for the Management of Patients With
Aneurysmal Subarachnoid Hemorrhage: A Guideline From
the American Heart Association/ American Stroke
Association
-Up To Date
-Lexi comp

63. Any Questions ☺☺

64. See you in next lecture CNS
infections

65. Thank You ☺
You can find me at
[email protected]
Mohamed Rawy
Mohamed Rawy (Roma)