Use the labels in the right column to find what you want. Or you can go thru them one by one, there are only 34,264 posts. Searching is done in the search box in upper left corner. I blog on anything to do with stroke. DO NOT DO ANYTHING SUGGESTED HERE AS I AM NOT MEDICALLY TRAINED, YOUR DOCTOR IS, LISTEN TO THEM. BUT I BET THEY DON'T KNOW HOW TO GET YOU 100% RECOVERED. I DON'T EITHER BUT HAVE PLENTY OF QUESTIONS FOR YOUR DOCTOR TO ANSWER.
Changing stroke rehab and research worldwide now.Time is Brain!trillions and trillions of neuronsthatDIEeach day because there areNOeffective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.
What this blog is for:
My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.
Showing posts with label subarachnoid hemorrhage. Show all posts
Showing posts with label subarachnoid hemorrhage. Show all posts
April 23 (Reuters) - Grace Therapeutics said on Thursday the U.S. Food and Drug Administration declined to approve its drug for a rare type of stroke, citing deficiencies in chemistry, manufacturing and controls and non-clinical data.
Shares of the Princeton, New Jersey-based company were down 43%.
In its complete response letter, the FDA referenced specific issues in the chemistry, manufacturing and controls (CMC) and non-clinical sections of the company's application. Grace said it can address these in a resubmission.
Those issues relate to leachables data for product packaging, non-clinical product toxicology risk assessments and product manufacturing deficiencies at the contract manufacturing organization, the company said.
Leachables are chemical compounds that migrate from packaging, manufacturing equipment or delivery systems into a drug.
The company said it intends to request a meeting with the FDA to clarify the path forward and determine the appropriate next steps.
"Potential FDA approval of ... GTx-104 for the treatment of aSAH would represent the first meaningful innovation in the standard of care for these patients in more than 40 years," said Prashant Kohli, Grace's CEO.
The drug GTx-104 is for the treatment of aneurysmal subarachnoid hemorrhage, a critical, often fatal form of stroke caused by a ruptured brain aneurysm.
Grace said it is a relatively uncommon type of stroke that accounts for about 5% of all strokes and an estimated 42,500 hospital-treated patients in the U.S.
GTx-104 is an injectable formulation of nimodipine, the only FDA-approved drug for aneurysmal subarachnoid hemorrhage, for intravenous infusion. The IV delivery has the potential to lower drug-to-drug interactions and eliminate potential dosing errors, Grace added.
(Reporting by Puyaan Singh in Bengaluru; Editing by Tasim Zahid)
Tracy A. Iona https://orcid.org/0009-0000-1033-2410, and
Shane W. English, MD https://orcid.org/0000-0002-9477-6146 senglish@toh.ca
on behalf of the SAH Core Domain Set and Core Domain Definitions Working Groups and the Canadian Critical Care Trials GroupAuthor Info & Affiliations
Stroke
New online
Abstract
The health outcomes currently reported in aneurysmal subarachnoid hemorrhage (aSAH) research lack consistency and do not sufficiently reflect what is important to people most affected. The objective of this article was to establish consensus on the aspects of health (domains) clinicians and researchers should measure in aSAH research.
METHODS:
Informed by 2 international prioritizing surveys (involving 239 participants from over 25 countries and 6 continents), we used established consensus methodology in a hybrid in-person/online consensus meeting to establish which domains of health researchers should measure in aSAH research. Sixty-nine participants with lived experience with aSAH (35%), clinical and research leaders (62%), or from aSAH-related charity (3%) took part. International multidisciplinary working groups established consensus definitions for each domain.
RESULTS:
Consensus (>70% endorsement) was sought on a proposed group of 6 domains of health, and failing that, each domain individually. The 6 domains which reached consensus and were formally defined are (1) health-related quality of life, (2) survival, (3) cognition and executive function, (4) functional outcome, (5) delayed cerebral ischemia and cerebral infarction, and (6) rebleeding and aneurysm obliteration.
CONCLUSIONS:
This International Position Statement reports the consensus process undertaken and the core domain set established to guide the choice of outcomes for evaluating new treatments for aSAH. It will ultimately help shape the future aSAH research agenda.
While the efficacy of statins, which are cholesterol-lowering agents, in preventing subarachnoid hemorrhage (SAH) has been examined in experimental animal models and some clinical studies, findings remain inconclusive. This study aimed to investigate the association between statin use and the risk of SAH.
METHODS:
We conducted a large population-based case-control study using data from the Japanese Health Insurance Claims Database from January 2005 to August 2021. This nationwide database includes the data of individuals aged 0 to 74 years. Cases were defined as patients hospitalized with a first diagnosis of SAH (International Classification of Diseases, Tenth Revision code I60) during this period. Four controls per case were randomly selected and matched by age, sex, and follow-up period using incidence density sampling. Statin exposure (use, recency, and duration) was evaluated before the incidence of SAH. Conditional logistic regression, adjusted for patient characteristics, was used to assess the association between statin use and SAH risk. We also investigated whether this association varies with a history of hypertension, diabetes, cerebrovascular disease, unruptured intracranial aneurysms, and the use of antihypertensive medications.
RESULTS:
The study identified 3498 cases and 13 992 matched controls. Statin use was reported in 12.2% of SAH cases and 12.7% of the controls. After adjusting for patient characteristics, statin use was associated with a significantly reduced risk of SAH (adjusted odds ratio, 0.81 [95% CI, 0.69–0.95]). The association was significantly influenced by a history of hypertension or cerebrovascular disease (P interaction=0.042 and 0.042, respectively).
CONCLUSIONS:
Statin use was significantly associated with a reduced risk of SAH. These findings suggest that statins may play a role in the prevention of SAH, particularly in patients with a history of hypertension or cerebrovascular disease.
If you blithering idiots would actually think you'd realize the solution is 100% recovery protocols! WHY THE FUCK AREN'T YOU WORKING ON THAT? STUPIDITY?
JAMA Neurol. Published online May 23, 2025. doi:10.1001/jamaneurol.2025.1522
Key Points
Question
What is the global burden of nontraumatic subarachnoid hemorrhage (SAH)?
Findings
Results of this cross-sectional study, based on the Global
Burden of Disease 2021 study, reveal that in 2021, there were 700 000
new SAH cases, almost 8 million patients with prevalent SAH(This is why you need 100% recovery protocols! Exact action can be done with this! Prevention can't be guaranteed. So the obvious solution is 100% recovery protocols! GET THERE!), 350 000 SAH
deaths, and over 10 million SAH-related disability-adjusted life-years
globally. Despite decreasing age-standardized burden rates, SAH remained
one of the most common cardiovascular and neurological causes of death
and disability in the world.
Meaning
Given the high proportional burden of SAH, study results
suggest evidence for the potential health benefits of proactive public
health planning and resource allocation for SAH prevention.
Abstract
Importance
Nontraumatic subarachnoid hemorrhage (SAH) represents the
third most common stroke type with unique etiologies, risk factors,
diagnostics, and treatments. Nevertheless, epidemiological studies often
cluster SAH with other stroke types leaving its distinct burden
estimates obscure.
Objective
To estimate the worldwide burden of SAH.
Design, Setting, and Participants
Based on the repeated cross-sectional Global Burden of Disease
(GBD) 2021 study, the global burden of SAH in 1990 to 2021 was
estimated. Moreover, the SAH burden was compared with other diseases,
and its associations with 14 individual risk factors were investigated
with available data in the GBD 2021 study. The GBD study included the
burden estimates of nontraumatic SAH among all ages in 204 countries and
territories between 1990 and 2021.
Exposures
SAH and 14 modifiable risk factors.
Main Outcomes and Measures
Absolute numbers and age-standardized rates with 95%
uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and
disability-adjusted life-years (DALYs) as well as risk factor–specific
population attributable fractions (PAFs).
Results
In 2021, the global age-standardized SAH incidence was 8.3
(95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality
was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6)
per 100 000 people. The highest burden estimates were found in Latin
America, the Caribbean, Oceania, and high-income Asia Pacific. Although
the absolute number of SAH cases increased, especially in regions with a
low sociodemographic index, all age-standardized burden rates decreased
between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%),
prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI,
40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300
diseases, SAH ranked as the 36th most common cause of death and 59th
most common cause of DALY in the world. Of all worldwide SAH-related
DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled
risk factors of which high systolic blood pressure (population
attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking
(PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution.
Conclusions and Relevance
Although the global age-standardized burden rates of SAH more
than halved over the last 3 decades, SAH remained one of the most common
cardiovascular and neurological causes of death and disabilities in the
world, with increasing absolute case numbers. These findings suggest
evidence for the potential health benefits of proactive public health
planning and resource allocation toward the prevention of SAH.
Described a problem, suggested further research, did not specify WHOM was going to accomplish that! Useless! I expect stroke researchers to solve problems; not just tell us they exist. With proper leadership stroke could easily be solved.
Subarachnoid hemorrhage (SAH) is a clinical condition with a high
mortality rate that causes in survivors’ permanent disabilities. Among
complications after SAH, the most important is the delayed large vessel
vasospasm, which have been intensively studied. It is usually seen after
day 3 of hemorrhage, and it could contribute to another complication
that is delayed cerebral ischemia (DCI). In contrast, arteriolar
vasospasm, known as microvasospasm, has been reported to occur in the
subacute phase, and it is believed to contribute to DCI. Delayed
vasospasm is usually treated with endothelin receptor antagonist drugs
(e.g., clazosentan sodium), which, however, cannot completely prevent
DCI. Few studies focused on the mechanism of microvasospasms, and no
studies have revealed pathological mechanisms underlying subacute
microvasospasms.
The aim of the study is to elucidate the mechanism of microvasospasm
through an animal model with intravital 2-photon microscopy,
investigating effects of neutrophil removal and, in particular, of
Neutrophil Extracellular Traps (NETs) released by neutrophils. NETs are
DNA histone complexes released by activated neutrophils, composed of DNA
and various antibacterial proteins that have the original purpose of
capturing and neutralizing pathogens. Despite that, NET can have a
disadvantage of damaging host cells, and, in particular, they are known
to play a crucial role in brain damage after SAH.
The author first established an SAH mouse model with a cranial window of 3 x 3 mm, as previously described.1,2
Briefly, they injected 40 uL of blood from the hearts of littermate
mice, in the prechiasmatic cistern using a syringe coated with a minimal
amount of heparin. Erythrocytes were previously labeled with
phycoerythrin (PE) or fluorescein isothiocyanate (FITC) to visualize
their distribution, and neutrophils were labeled with a PE-conjugated
anti Ly6G antibody. All was visualized and recorded by time-lapse
imaging through 2-photon microscopy. Of course, sham animals underwent
the same procedure except for blood injection. The authors observed that
both cells population were distributed to the perivascular space of the
pial arterioles. Erythrocytes disappeared gradually and almost
completely after 2 to 5 days. Concurrently, the pial arterioles were
constricted and appeared as microvasospam, as illustrated in Figure 1F.
Figure 1E-F.
The source of infiltrating neutrophils was checked through the use of
LysM EGFP reporter mice in which neutrophils robustly express a green
fluorescent protein: The authors verified that the source of neutrophil
infiltration was the circulation of the host but not the injected blood.
The authors then depleted neutrophils from the host mice by
intraperitoneal administration of neutrophil-specific antibody (200 ug
of rat anti-Ly6G antibody) 1 day and 1 hour before SAH, and then
evaluated microvasospasms, visualized as pearl-string-like stenosis:
Microvasospasms were significantly reduced in the neutrophil depleted
group. For the control group, an equal amount of the isotype control was
injected. Nakagawa and colleagues observed that in the control group,
the number of infiltrating neutrophils was correlated with the volume of
accumulated erythrocytes, speculating that neutrophil infiltration in
the perivascular space may have been triggered by erythrocyte
accumulation.
Focusing on NETs formation, to confirm their presence in the
perivascular space, a marker for NETs (SYTOX Green) was intracisternally
injected, indicating that, after SAH, NETs are released in the
perivascular space. To test if NETs cause microvasospasm, the authors
administered DNase, a NETs inhibitor, at 1 day after SAH in order to
remove them in perivascular space. As expected, microvasospasms were
significantly suppressed after DNase treatment, and blood flow velocity
at day 5 significantly improved.
In conclusion, the author established an experimental system to
investigate events occurring after SAH, demonstrating accumulation of
erythrocytes in the perivascular space, the subsequent infiltration of
neutrophils, and, for the first time, the presence of a large amount of
NETs, leading to the development of microvasospasm. NETs were, in fact,
attached to the arterioles, suggesting that they may directly damage the
endothelium or vascular smooth muscle of the arterioles.
Some limitations of the study are due to the limited cranial window
to observe a relatively small part of the cerebral cortex, so results
may not be generalizable to the entire brain. Furthermore, there is a
need for additional research to verify the precise nature of
perivascular NETS and their pathological effects.
Is your competent? hospital keeping up with stroke research and writing protocols on their use? NO? So you don't have a functioning stroke hospital? Why hasn't the board of directors reconstituted the whole hospital then? They are incompetent also?
Moderate to severe angiographic vasospasm was detected more often in controls than in those given implants.
At 52 weeks, favorable outcomes were noted in 12 of 18 controls and in 16 of 19 patients given implants.
Use of nicardipine release implants during surgical aneurysm repair
was safe, efficacious and led to better outcomes compared with standard
care alone, according to research published in JAMA Neurology.
“So far, oral systemic nimodipine represents the only
guideline-recommended pharmacologic therapy for the prevention of a
[vasospasm]-associated [delayed cerebral ischemia], but remains hampered
by limited effectiveness,” Lars Wessels, MD, a physician in the department of neurosurgery, Charite-University Medical Center Berlin, and colleagues wrote.
Recent research determined that employing nicardipine implants
during aneurysm surgery was safe, effective and prevented angiographic
vasospasm after aneurysmal subarachnoid hemorrhage.Image: Adobe Stock
As cerebral vasospasm likely leads to suboptimal outcomes following aneurysmal subarachnoid hemorrhage
(aSAH), Wessels and colleagues sought to examine the safety and
efficacy of localized nicardipine release implants in those at risk for
developing proximal vasospasm after aSAH.
Their phase 2b, single-masked multicenter, randomized clinical trial
was conducted at six academic neurovascular centers in Germany and
Austria, and included 41 individuals with World Federation of
Neurological Surgeons grade 3 or 4 aSAH due to a ruptured anterior
circulation that required microsurgical aneurysm repair. Participants
were randomly assigned 1:1 within 48 hours of the rupture to receive
either 10 implants at 4 mg of nicardipine each plus standard of care
(implant group) or aneurysm repair alone plus standard of care (control
group).
The study’s primary endpoint was the incidence of moderate to severe
cerebral angiographic vasospasm (aVS) between days 7 and 9 following the
initial aneurysm rupture, while the primary safety endpoint was the
occurrence of any adverse events following randomization that may not
have been caused by the treatment. The primary efficacy analysis
included 39 participants.
According to the results, between 7 to 9 days post rupture, moderate
or severe aVs was detected in 11 of 19 individuals in the control group
compared with four of 20 in the implant group. Concurrently, vasospasm
rescue surgery was required in two of 20 patients randomized to receive
the implant and 11 of 19 among the controls.
Data further show that, up to day 21, 180 treatment-adverse events were logged (implant group, n = 84; controls, n = 96), while new cerebral infarcts
were noted in six of 19 individuals in the control group and in two of
20 in the implant group. At 52 weeks, favorable outcomes were noted in
12 of 18 patients in the control group and 16 of 19 patients in the
implant group.
“Our findings regarding the magnitude of the intensive care unit stay
in the implant group ... may justify the use of nicardipine implants
from an economic health care standpoint,” Wessels and colleagues wrote.
Disclosures:
Wessels reports receiving travel expenses from BIT Pharma during
the conduct of the study. Please see the study for all other authors’
relevant financial disclosures
The
publication of the 2023 American Heart Association (AHA) Guidelines for
the Management of Aneurysmal Subarachnoid Hemorrhage represents a
milestone in the evolving landscape of cerebrovascular medicine.1
In this commentary, we aim to examine the fundamental shifts brought
into focus by these updated guidelines, highlighting the pivotal roles
of neuroendovascular management and the neurocritical intensive care
unit (neuro‐ICU). While neurointerventionalists have traditionally
played a pivotal role in the management of this condition, these
guidelines now expand their responsibilities beyond the confines of the
operating room.
Traditionally, aneurysmal
subarachnoid hemorrhage (aSAH) management has been centered around the
timely repair of ruptured cerebral aneurysms. Indeed, the urgency of
preventing rebleeding and securing the aneurysm cannot be overstated, as
it most significantly impacts patient outcomes. However, the 2023 AHA
Guidelines introduce a paradigm shift by recognizing that the battle
against aSAH is 2‐fold. While aneurysm repair remains a critical front,
there is a more equitable consideration of securement modality.
Furthermore, the neuro‐ICU emerges as an equally vital theater where the
clinical outcome is determined.
Guiding Precision Care and Tailoring Treatment: Neuroendovascular Techniques at the Forefront
The
updated guidelines for managing aSAH emphasize the importance of
personalized treatment strategies that consider the unique
characteristics of each aneurysm.1
Extensive research, exemplified by landmark studies such as the ISAT
(International Subarachnoid Aneurysm Trial) and the BRAT (Barrow
Ruptured Aneurysm Trial), has provided compelling evidence in favor of
coiling as the preferred method, particularly for improving patient
outcomes in the critical first year following treatment. However, the
landscape of aneurysm management is far from 1‐size‐fits‐all, and these
guidelines acknowledge the need for a tailored approach(So guessing).
Timing of Treatment
These guidelines stress the significance of prompt intervention for aSAH.1
Whether through open surgery or endovascular procedures, treating the
ruptured aneurysm as early as possible after presentation, preferably
within 24 hours, is strongly recommended. This emphasis on timely care
reflects the evolving landscape of aneurysm treatment, where precision
and expeditiousness are central to achieving the best results for
patients. This recommendation is classified as class I, supported by
level B‐NR (nonrandomized) evidence. Delaying treatment, particularly
beyond a 3‐day window, is discouraged.
Treatment Goal
The primary objective in treating patients with aSAH is the complete obliteration of the ruptured aneurysm whenever feasible(Why not 100% recovery? That's what all survivors want?).1
This strategy is advocated to reduce the risk of rebleeding and the
need for retreatment. In cases for which immediate complete obliteration
is not achievable, partial obliteration to secure the rupture site is
an acceptable strategy(So failure is acceptable? Good to know!), with retreatment considered for those displaying
functional recovery. This recommendation is also classified as class I,
with level B‐NR evidence.
Modality of Treatment for Posterior Circulation Aneurysms
These guidelines provide specific guidance for aSAH resulting from ruptured aneurysms in the posterior circulation.1
In cases in which coiling these aneurysms is feasible, it is
recommended over surgical clipping to enhance patient outcomes. This
partiality is supported by class I evidence with level B‐R (randomized).
Emergency Clot Evacuation
For
patients with aSAH considered salvageable but presenting with a
depressed level of consciousness due to a large intraparenchymal
hematoma, emergency clot evacuation is recommended.1 This intervention is pivotal in reducing death and is classified as a class I recommendation with level B‐R evidence.
Specialist Evaluation
The
guidelines underline the importance of involving specialists with
expertise in both endovascular and surgical treatments for evaluating
ruptured aneurysm.1
This assessment is essential for determining the most suitable
treatment approach tailored to individual patient and aneurysm
characteristics. Although categorized as class IIb, this recommendation
is supported by level B‐R evidence.
Age‐Specific Considerations
Age plays a crucial role in treatment decisions for patients with aSAH.1
The efficacy of coiling or clipping in improving outcomes for
individuals aged >70 years is uncertain, marked as a class IIb
recommendation with level C‐LD (limited data) evidence. Conversely, for
patients aged <40 years, surgical clipping of the ruptured aneurysm
may be considered preferable to enhance treatment durability and overall
outcome.
Modality of Treatment for Equally Suitable Aneurysms
In
cases of good‐grade aSAH stemming from ruptured aneurysms in the
anterior circulation, where primary coiling and clipping are both
viable, the 2023 AHA guidelines endorse primary coiling for superior
1‐year functional outcomes.1
Supported by level A evidence, this recommendation holds a class I
designation. However, both treatment options are considered reasonable
to achieve favorable long‐term outcomes, constituting a class IIa
recommendation with level B‐R evidence.
Endovascular Advancements
These
guidelines underscore the growing acceptance of advanced techniques in
aneurysm treatment, particularly for wide‐neck aneurysms resistant to
traditional methods.1 Notably, stent‐assisted coiling and flow diversion have gained favor.
Use of Flow Diverters for Fusiform/Blister Aneurysms
In
cases of aSAH from ruptured fusiform or blister aneurysms, the use of
flow diverters is considered reasonable to reduce death, as indicated by
a class IIa recommendation with level C‐LD evidence.1
Stents or Flow Diverters for Saccular Aneurysms
It
is crucial to note, however, that for patients with aSAH with ruptured
saccular aneurysms suitable for either primary coiling or clipping, the
guidelines advise against using stents or flow diverters due to a higher
risk of complications.1
This recommendation is classified as class III, indicating harm, with
level B‐NR evidence. In such instances, where coiling is not deemed
suitable or when there is a state of equipoise, the guidelines emphasize
the importance of comprehensive multidisciplinary discussions. These
discussions should carefully weigh the merits of both neurosurgical and
neuroendovascular alternatives, considering each patient's unique
circumstances and clinical presentation.
In
summary, these guidelines represent a significant step forward in
tailoring aSAH treatment to individual patient needs. By emphasizing
precision and timeliness in intervention, they aim to achieve the best
possible outcomes for patients facing this critical medical condition.
The growing acceptance of advanced techniques reflects the dynamic
nature of aneurysm management, highlighting the importance of staying
abreast of evolving treatment options and engaging in thoughtful,
multidisciplinary discussions to optimize patient care.
The Rise of Neurocritical Care
The
neuro‐ICU has, in recent years, transitioned from a supporting role to
taking center stage in aSAH management. This change is not arbitrary; it
is substantiated by a growing body of evidence that underscores the
importance of specialized critical care for patients with aSAH.2
Multidisciplinary teams in neuro‐ICUs have been shown to significantly
enhance patient survival and improve overall outcomes. These teams bring
together neurointensivists, neurosurgeons, interventionists, nurses,
and other specialists, working in concert to provide the highest
standard of care.
The rationale behind this
shift is also founded on comparative effectiveness research that
consistently demonstrates the benefits of specialized neurocritical
care.3
High‐volume centers equipped with dedicated neuro‐ICUs have
consistently reported lower mortality rates and improved patient
outcomes. This is not merely a theoretical concept but a practical
reality that demands acknowledgment and implementation.
Ultimately,
the 2023 AHA guidelines serve as a call to action for the medical
community, urging physicians, hospitals, medical societies, and national
organizations to recognize and champion the importance of neuro‐ICUs in
aSAH management.1
With these guidelines, it is recognized that comprehensive care for
patients with aSAH encompasses not only surgical prowess but also the
intricate and specialized care delivered within the neuro‐ICU.
Refresher on Mechanical Ventilation
The
2023 guidelines sought to reduce the duration of mechanical ventilation
and the risk of hospital‐acquired pneumonia, recognizing that optimal
outcomes for critically ill ventilated patients are more likely when
evidence‐based care bundles are applied.1
For patients experiencing aSAH who require mechanical ventilation for
>24 hours, it is strongly recommended to implement a standardized ICU
care bundle. This recommendation underscores the importance of drawing
from the extensive research conducted in both medical and surgical ICUs
and consistently applying these principles to patients with high‐grade
aSAH (HG‐aSAH). The core components of the ventilator bundle, often
referred to as “ABCDEF,” encompass the following aspects:
•
Assess, prevent, and manage pain
•
Both spontaneous awakening trials and spontaneous breathing trials
•
Choice of analgesia and sedation
•
Delirium: assess, prevent, and manage
•
Early mobility and exercise
•
Family engagement and empowerment
In
practical terms, what this means for patients with HG‐aSAH is 2‐fold.
First, there is substantial evidence supporting the reduction in the use
of opioid narcotics and a preference for nonsteroidal anti‐inflammatory
drugs like acetaminophen, ibuprofen, and ketorolac.4
Second, it involves the regular interruption of sedation, at least once
daily, to assess the patient's neurological status and prevent
excessive sedation.
Effective prevention of
delirium, a common challenge after aSAH, is achieved by avoiding
benzodiazepine sedation. Instead, dexmedetomidine is recommended for
achieving light sedation while also helping to manage the autonomic
dysregulation (ie, storming) often seen in these patients.5
Finally, systematic early mobilization necessitates a substantial
commitment from both physical therapy and nursing teams. For example,
every Hunt–Hess grade III patient capable of following commands with an
external ventricular drain should be ambulated daily. These initiatives
are best organized and led by a dedicated team of neurointensivists.
Advancements in Neuromonitoring
The
updated guidelines emphasize the importance of employing advanced
monitoring techniques in the management of patients with HG‐aSAH,
particularly when their neurological examination is limited.1
The direction of neurocritical care, especially for severe brain
injuries like HG‐aSAH, is undeniably moving toward sophisticated
multimodality brain monitoring. The foundation of this approach involves
initiating long‐term continuous video electroencephalogram monitoring, a
practice that should be maintained for at least 48 hours in all
comatose patients, including those with HG‐aSAH.6
Studies
have indicated that nonconvulsive seizures are more prevalent in this
patient population than previously thought, with a frequency ranging
from 10% to 30%.7
Importantly, there is substantial evidence to suggest that
electrographic seizure activity can significantly impact the patient's
level of consciousness and exacerbate secondary brain injury.
Furthermore, nonconvulsive seizures have been identified as potential
mimics of delayed cerebral ischemia (DCI) after aSAH.8, 9
In
recent years, there has been a notable surge in interest and research
dedicated to neuromonitoring techniques, encompassing both invasive and
noninvasive approaches. One particularly intriguing noninvasive method
is transcranial Doppler, often likened to a highly sophisticated
ultrasound for the brain. It stands out with an impressive sensitivity
exceeding 90%, making it a valuable bedside tool for detecting cerebral
abnormalities. However, it is equally important to acknowledge the
inherent limitations of this technique. While it excels in sensitivity,
it exhibits a specificity of 71% and is also limited by a positive
predictive value of 57%. These statistics underscore the need for
cautious interpretation and consideration of other clinical factors when
using transcranial Doppler data.
Quantitative electroencephalogram patterns have emerged as another noninvasive neuromonitoring approach with great potential.1
These patterns have shown promise in detecting DCI, with supporting
evidence from prospective studies suggesting their clinical relevance.
The ability to noninvasively identify DCI is a significant step forward
in managing patients with complex neurological conditions.
Invasive
neuromonitoring tools, such as brain tissue oxygen monitoring, cerebral
microdialysis, and electrocorticography, have also found their place in
the realm of DCI detection.1
This assertion is supported by a comprehensive review encompassing 47
studies. These invasive techniques provide valuable insights into
cerebral physiology and can be instrumental in tailoring treatment
strategies for individual patients.
In
summary, it is important to recognize that the optimal indications and
best practices for these neuromonitoring methods are still under
investigation. The field continues to evolve as researchers refine their
understanding of when and how to deploy these techniques most
effectively. Moreover, while these tools hold great promise, their
ultimate impact on clinical outcomes in the context of subarachnoid
hemorrhage and other neurological conditions remains an area of active
exploration.
Antiseizure Medication Controversy
One
contentious topic within the management of aSAH that the guidelines
grapple with is the use of prophylactic antiseizure medications.1
While the guidelines do recommend against their routine administration,
they do so with an understanding that numerous medical centers continue
to adopt a universal approach in administering these medications to
patients with aSAH. This disparity in practice highlights the ongoing
debate surrounding the benefits and risks associated with prophylactic
antiseizure medications in this patient population, particularly in
relation to cognitive outcomes.
The rationale
for administering prophylactic antiseizure medications stems from
concerns about the heightened risk of seizures in patients with aSAH due
to the brain's exposure to blood and potential irritants from the
hemorrhage. Consequently, some medical institutions have chosen to err
on the side of caution by providing antiseizure medications to all
patients with aSAH, regardless of their individual risk factors.
Although antiseizure medications can effectively reduce the risk of
seizures, they are not without their own set of adverse effects. These
medications may lead to side effects such as sedation, impaired
cognition, and even delirium.
There is a
growing body of evidence suggesting that long‐term use of certain
antiseizure medications, particularly phenytoin, may be associated with
negative cognitive outcomes in patients with aSAH.1
This raises concerns about whether the potential benefits in terms of
seizure prevention outweigh the risks, especially when it comes to the
patient's overall cognitive function and quality of life. The cumulative
risk of convulsive seizures in hospitalized patients with aSAH has been
reported to be 4%. Could the risk of delirium or oversedation from
routine antiseizure medication use be higher? It has been reported that
continued phenytoin use after discharge in patients with aSAH is
associated with worse cognitive outcomes that then improve when the
medication is stopped. We do not anticipate any change in practice until
clinical trials are conducted to address the issue of antiseizure
medication use after aSAH.
The guidelines acknowledge this contentious landscape and the need for further clarity.1
They highlight the importance of conducting additional clinical trials
to better understand the impact of prophylactic antiseizure medications
on cognitive outcomes in patients with aSAH. This research would aim to
provide concrete evidence regarding the risk–benefit balance,
potentially informing more precise recommendations in the future.
Caution Against Hemodynamic Prophylaxis and Hypervolemia
The
cautionary approach to hemodynamic augmentation and hypervolemia in the
2023 AHA Guidelines for aSAH management signifies another notable
departure from previous strategies.1
This shift aligns with a broader principle in critical care medicine:
the recognition that sometimes less intervention can yield better
outcomes. It reflects the acknowledgment that excessive medical
interventions, even with the best intentions, can lead to unintended
complications that may worsen the patient's condition.
One
of the critical aspects of this cautionary approach is the recognition
of potential complications associated with aggressive hemodynamic
management.10
By attempting to artificially increase blood pressure or volume in
patients with aSAH, health care providers may inadvertently trigger an
adverse event. In certain circumstances, we may develop a strong
fixation on pursuing active interventions, making it quite tempting to
deviate from established protocols. For instance, one might consider, “I
know that per the guidelines we're only supposed to induce hypertension
in the face of symptomatic vasospasm, but I'm concerned about this
particular patient.” In addition to potentially fatal complications such
as myocardial infarction and pulmonary edema, the guidelines highlight
the risk of exacerbating intracranial pressure, which can be detrimental
in patients with aSAH, who are already at risk of elevated pressure
within the skull. Additionally, there is the practice of
prophylactically inducing hypertension to arbitrary blood pressure
targets in every patient. This is a common occurrence.
Another
noteworthy concern is the possibility of inducing posterior reversible
encephalopathy syndrome, a neurological condition characterized by
symptoms such as headache, altered mental status, seizures, and visual
disturbances. Posterior reversible encephalopathy syndrome can occur
when there is a sudden increase in blood pressure, which can result from
aggressive attempts to elevate it in patients aSAH. Recognizing the
potential harm of such interventions is crucial in avoiding these
complications.
As a final deterrent from aggressive hemodynamic management, the guidelines draw attention to the concept of pressor dependence.1
This phenomenon is thought to occur when patients are subjected to
aggressive blood pressure management, resulting in their bodies becoming
reliant on medications to sustain blood pressure within a reasonable
target range. This can make it challenging to wean patients off these
medications without their blood pressure dropping below the desired
threshold. Even if only occurring in the thoughts and concerns of the
neuro‐ICU team, this phenomenon can lead to prolonged hospital stays and
increased health care resource usage.
More Oral Nimodipine?
With
a continuance of the 2012 recommendations, the updated guidelines stamp
the significance of early enteral nimodipine initiation in preventing
DCI and enhancing functional outcomes in cases of aSAH.1
In
clinical practice, the administration of oral nimodipine occurs along a
schedule of 60 mg every 4 hours, following the precedent set by the
British Nimodipine Trial in 1989.11
Unfortunately, this regimen often gets discontinued as soon as patients
with aSAH exhibit symptomatic vasospasm due to its tendency to cause
systemic hypotension. As a result, health care providers often resort to
halving the dosage or, more commonly, suspending nimodipine altogether.
The
question that has persisted over time is whether there might be
superior agents or administration protocols for arterial vasodilators
that could provide more effective alternatives.1
Examples include continuous intravenous infusion of nimodipine, a
practice prevalent in Europe, or the use of fasudil and clazosentan,
which are favored in Japan. However, it is crucial to note that the
current body of evidence does not support an immediate shift in US
clinical practice. This underscores the dynamic nature of medical
practice, with a recognition that as science advances, treatment
strategies may evolve to provide better outcomes for patients with aSAH.
Taking the Guidelines Into Practice
In
managing cases of aSAH, it is crucial to recognize that there is not a
definitive volume threshold that guides treatment decisions. Each
patient's condition must be carefully evaluated, highlighting the
importance of individualized care. Timely transfer of patients
presenting with acute severe headaches or new neurological deficits is
paramount to ensure they undergo appropriate diagnostic assessments and
receive specialized care as needed. Patients presenting >6 hours
after the onset of severe headaches or those with new neurological
deficits should undergo a noncontrast head computed tomography. If this
initial scan is negative for aSAH, lumbar puncture becomes essential to
confirm or exclude the presence of subarachnoid blood. Similarly, for
individuals with spontaneous aSAH and a strong suspicion of aneurysmal
involvement but inconclusive results from computed tomography
angiography, digital subtraction angiography is the recommended
diagnostic tool to identify or rule out cerebral aneurysms promptly.
Prompt identification of aneurysmal sources remains a paramount concern for clinical management.1
Comprehensive use of advanced imaging methods, such as CT angiography,
can significantly aid in this regard. Furthermore, using established
grading scales can aid in outcome prediction and guide discussions with
patients, families, and surrogates regarding treatment choices.
Decisions regarding the treatment of ruptured aneurysms should be made
by specialists well versed in both endovascular and surgical approaches.
Ultimately, the determination to use clipping, coil embolization, or
even flow diversion should be tailored to the patient's distinctive
characteristics and the aneurysm's unique features. As highlighted by
the current guidelines, there is a growing preference for coil
embolization for good‐grade aSAH cases originating from anterior
circulation ruptured aneurysms.1
Neuro‐ICU
management should encompass preventive measures such as deep vein
thrombosis prophylaxis, maintaining euvolemia, and thoughtful fluid
management.1
While invasive neuromonitoring techniques are increasingly valuable for
detecting DCI in high‐grade aSAH cases, the specific goals for fluid
management require further clarification. Although the risk of rerupture
in aSAH cases is relatively low, the use of imaging to guide treatment
decisions for survivors in the neuro‐ICU is recommended, particularly in
individuals with residual aneurysms. Regular monitoring for the
development of new aneurysms is also essential, especially in younger
patients with multiple aneurysms or a strong family history of aSAH.
Additionally, considerations
such as the timing of cerebrospinal fluid diversion, choice of fluids,
sodium goals, temperature management, glucose control, and monitoring of
intracranial pressure and multimodal monitoring are important aspects
of comprehensive aSAH management that deserve further attention and
investigation.1
Finally, early identification of deficits, especially in behavioral and
cognitive domains, is crucial. Interventions for mood disorders can
significantly improve long‐term outcomes, and providing counseling on
the higher risk of long‐term cognitive dysfunction may prove beneficial
for patients recovering from aSAH.
