Keywords
neurocritical care - neuroanesthesia - craniotomy - stroke
Cerebrovascular Disease
Aneurysmal Subarachnoid Hemorrhage and Delayed Cerebral Ischemia
Cerebral vasospasm and delayed cerebral ischemia (DCI) are common and potentially
devastating complications of aneurysmal subarachnoid hemorrhage (aSAH) and are associated
with poor neurological outcomes. However, high-quality evidence supporting various
aspects of monitoring and management of DCI is limited.[1]
[2]
Picetti et al conducted an international clinical practice survey aimed at identifying
strategies for diagnosing, monitoring, preventing, and managing cerebral vasospasm
associated with DCI in aSAH patients requiring intensive care unit (ICU) admissions
(The Mantra Study).[3] The survey was conducted online and involved 292 medical professionals from 240
centers spanning 38 countries. The survey questionnaire was designed to identify methods
of diagnosing, monitoring, preventing, and managing DCI related to cerebral vasospasm
at the respondents' respective centers.
Neurological examination was most frequently used to diagnose delayed neurological
deficits caused by vasospasm-related DCI in awake aSAH patients or those able to tolerate
interruption of sedation (95.2%), followed by transcranial Doppler (TCD) (60.3%) and
intracranial pressure (ICP) monitoring (29.5%). In unconscious patients or those unable
to tolerate sedation interruption, TCD was the diagnostic tool of choice (68.5%).
In both scenarios, computed tomography (CT) angiography was most used to confirm vasospasm
as the cause of neurological deficits related to DCI (58.6% in the former; 54.5% in
the latter). Bedside monitoring for vasospasm in both asymptomatic and symptomatic
patients was routinely done using TCD by most respondents (61% for the former, 63.4%
for the latter). A large majority of respondents administer nimodipine for DCI prophylaxis.
Treatment of angiographic vasospasm was generally initiated only if associated with
clinical signs. Few utilized multimodal neuromonitoring to guide therapy. Most respondents
induced arterial hypertension as the first step to treat vasospasm, with the vasopressor
of choice being noradrenaline. The most common second step in treating vasospasm was
intra-arterial nimodipine administered in the angiography suite. Despite it being
an international survey, the number of respondents was low. Most respondents were
from higher-income nations; therefore, the result of the survey reflects practices
in more advanced health care systems. Nevertheless, it demonstrates the heterogenicity
in monitoring and management practices of DCI related to vasospasm in aSAH patients
and highlights the need to develop protocols based on resource availability.
Blood Pressure Management in Patients with Aneurysmal Subarachnoid Hemorrhage
The American Heart Association (AHA) and American Stroke Association (ASA) have developed
guidelines recommending elevation of blood pressure (BP) to reduce the progression
of DCI.[4] However, no large-scale randomized controlled trials (RCTs) have investigated this,
or is there a clear definition of induced hypertension. Betteridge et al performed
a post hoc analysis on data collected from the prospective multicenter observational
study of aneurysmal subarachnoid hemorrhage (PROMOTE-SAH).[5] The purpose of this study was to outline BP management goals (setting of a minimum
systolic BP [SBP] target or application of induced hypertension) in these patients
and evaluate whether setting BP management targets was independently linked to functional
outcomes at 6 months. Three hundred and fifty-seven patients with acute aSAH requiring
ICU admission were enrolled in 11 neurosurgical referral centers in Australia and
New Zealand. BP management goals were defined as subjects having either (1) a minimum
SBP target recorded or (2) classified as receiving induced hypertension for the management
of DCI or vasospasm. The primary study outcome was a modified Rankin Scale (mRS) score
of ≥ 4 (dead or disabled) at 6 months. The study showed that BP management goals are
commonly “prescribed” to aSAH patients admitted to ICUs across Australia and New Zealand
(75% of the study cohort). These goals were applied regardless of the presence of
DCI and/or vasospasm. The overall population mean minimum SBP target was 130 mm Hg
(128–133 mm Hg; confidence interval [CI] 95%). The mean (interquartile range) minimum
SBP target was significantly higher in patients with DCI/vasospasm (144 [142, 147]
mm Hg) than for those without (124 [122, 126] mm Hg; p < 0.001). The study only reported the setting of BP goals rather than the actual
BP achieved, which is one of its limitations. With regards to the primary outcome,
the unadjusted analysis demonstrated an association between the setting of goals for
BP management and reduced “death or disability” at 6 months. However, they found that
this benefit did not persist with adjusted analysis. The researchers concluded that
although BP management goals in critically ill patients with aSAH are common in Australia
and New Zealand, its impact in various clinical scenarios remains unclear.
Statin Treatment in Patients with Subarachnoid Hemorrhage
Considerable research has been done on various classes of drugs to investigate their
roles in reducing the risk of DCI in patients with aSAH. One of the classes of drugs
is statins for their antispastic effect on affected vessels through activation of
endothelial nitric oxide expression.[6] The 2023 AHA/ ASA SAH guideline does not recommend statins as routine therapy in
this population due to the lack of strong evidence demonstrating its efficacy on DCI
and mortality.[4]
Wang et al conducted a network meta-analysis that sought to investigate the therapeutic
benefits of different statin treatments in patients presenting with aSAH.[7] The investigators analyzed 13 two-group trials involving 1,885 patients where different
doses of atorvastatin, pravastatin, and simvastatin versus a placebo treatment were
administered for various durations. They observed that high-dose therapy (pravastatin
40 mg, simvastatin 80 mg) was associated with reduced risk of DCI compared with placebo
(relative risk [RR] 0.70, 95% CI 0.60–0.80). Their analysis also suggested that short-term
therapy (2 weeks) might confer more benefits than long-term therapy (RR 0.62, 95%
CI 0.50–0.76). However, the certainty of evidence ranged from low to moderate, at
best. The authors were also unable to perform subgroup analysis or meta-regression
due to insufficient data. Further research, specifically ones featuring extended follow-up
periods, is imperative to validate these findings.
Risk Factors for Delayed Postoperative Hemorrhage after Brain Arteriovenous Malformation
Resection
One of the most feared complications of microsurgical resection of brain arteriovenous
malformations (AVMs) is delayed postoperative hemorrhage (DPH), as it is associated
with significant morbidity and mortality.[8] Identification of risk factors for DPH could allow clinicians to take preemptive
measures to reduce its incidence. Yan et al conducted a retrospective study to identify
the risk factors for DPH in patients who underwent microsurgical resection for AVM.[9] A total of 1,284 patients were included in the study. DPH was defined as postoperative
intracerebral hemorrhage (ICH) into the AVM bed within 14 days after AVM resection
that resulted in neurological decline or reoperation for evacuation. The incidence
of DPH in this series was 1.4%. Univariate analyses identified several characteristics
in vascular architecture that were more likely to be associated with DPH events, which
include a giant nidus, a nidus involved in the eloquent area, a periventricular nidus,
and a nidus accompanied by venous ectasia. The multivariate analysis identified maximum
AVM diameter (odds ratio [OR] 1.44 per 1-cm increase, 95% CI 1.13–1.83) and periventricular
lesion (OR 4.10, 95% CI 1.33–12.59) as independent factors associated with DPH. The
cutoff value for the maximum AVM diameter was 4.15 cm. Patients with an AVM with a
maximum diameter of ≥ 4.15 cm had a higher DPH risk after surgery (hazard ratio [HR]
5.79, 95% CI 2.01–16.67; p < 0.01). Similarly, the incidence of DPH for patients with periventricular lesions
was higher than that for patients without periventricular lesions (HR 4.50, 95% CI
1.77–11.40; p < 0.01). In addition, the authors advocate the following strategies, namely, BP control,
preoperative embolization, intraoperative monitoring, and careful patient selection
to reduce the incidence of DPH in high-risk patients.
Decompressive Craniectomy for Intracerebral Hemorrhage
Decompressive craniectomy (DC) has been shown to reduce mortality and improve functional
outcomes in patients with malignant middle cerebral artery infarction.[10] It remains unknown whether DC is beneficial in patients with spontaneous severe
deep ICH. The SWITCH (Swiss trial of decompressive craniectomy versus best medical
treatment of spontaneous supratentorial intracerebral hemorrhage) trial investigated
whether DC combined with the best medical treatment improves outcomes at 6 months
in adults (19–75 years) with severe deep ICH involving the basal ganglia or thalamus,
compared with the best medical treatment alone.[11] The study was conducted across 42 stroke centers in nine European countries. The
primary outcome of this trial was a poor clinical score (mRS 5–6) at 180 days. However,
the trial was stopped early due to funding constraints, with only 201 (out of a planned
300) participants enrolled between October 2014 and April 2023. Of the 197 participants
who provided delayed consent, 96 received DC plus the best medical treatment, and
101 received the best medical treatment alone. At 180 days, 44% of the DC plus best
medical treatment group and 58% of the medical treatment alone group had a poor mRS
score (adjusted risk ratio [aRR] 0.77, 95% CI 0.59–1.01, adjusted risk difference
−13%, 95% CI −26 to 0, p = 0.057). In the per-protocol analysis, 47% of the DC plus best medical treatment
group and 60% of the medical treatment group had poor outcomes (aRR 0.76, 95% CI 0.58–1.00).
Severe adverse events occurred in 41 and 44% of participants in the two groups, respectively.
The results suggest weak evidence that DC plus the best medical treatment may be superior
to medical treatment alone. However, survival was associated with severe disability,
irrespective of treatment groups. The findings of SWITCH apply specifically to a subgroup
of people with severe deep ICH and cannot be generalized to people with ICH in other
locations. There were many limitations in this study, including underpowered to detect
significant differences, uneven randomization rates across the sites, potential changes
in standards of care, and issues with blinding. Further research is needed to clarify
the potential benefits and risks of DC for this population.
Anesthesia for Endovascular Thrombectomy
The choice of anesthetic technique (general anesthesia [GA] vs. conscious sedation
[CS]) for endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) is a topic
of continuing debate. Consensus statements from the Society for Neuroscience in Anesthesiology
and Critical Care and guidelines from the AHA/ASA recommend an individualized choice
of anesthetic technique.[12]
[13]
A recent meta-analysis by Al-Salihi et al comprehensively reviewed 8 RCTs with a total
of 1,203 patients who underwent EVT for AIS.[14] In this meta-analysis, the authors analyzed functional independence outcomes (mRS
0–2), recanalization rates, mortality, and change in National Institutes of Health
Stroke Scale (NIHSS) score (24 hours and after 7 days). The study showed that GA had
better recanalization than CS (RR and 95% CI were 1.13 [1.07, 1.20], p > 0.001). Interestingly, despite this significant difference in recanalization rates,
functional independence (mRS 0–2) showed no significant difference between GA and
CS (RR and 95% CI were 1.10 [0.95, 1.27], p = 0.19). Excellent recovery (mRS 0–1) and poor recovery (mRS 3) outcomes were also
similar between the two groups. Furthermore, the authors' analysis indicated no statistically
significant difference between GA and CS regarding mortality rates during hospitalization
or at 3 months, or with NIHSS score at the 24-hour and 7-day time points. The observed
superior recanalization rates have noteworthy clinical implications. However, due
to the lack of significant differences in the other outcomes and its limited sample
size, further large-scale RCTs are necessary to validate these findings and inform
clinical decision-making.
Although studies have demonstrated the noninferiority of GA compared with CS for EVT,
the choice of anesthetic agent and intraoperative hemodynamic targets during GA are
areas of ongoing debate.[14] Crimmins et al investigated whether clinical outcomes in patients undergoing EVT
for AIS differ based on the anesthetic agent (propofol-based total intravenous anesthesia
vs. volatile agents).[15] They also evaluated the impact of mean arterial pressure (MAP) thresholds on outcomes.
In this retrospective observational study, 93 patients who received propofol or volatile
GA for EVT between 2015 and 2018 were included in this study. There was no difference
in the rate of favorable outcome (mRS 0–2) between the volatile and propofol groups
(48.8% vs. 55.8%, respectively; p = 0.5). Ninety-day mortality was lower in patients receiving propofol (11.5%) than
in those receiving volatile GA (29.3%) (OR 0.32; 95% CI 0.11–0.94; p = 0.03); this mortality benefit was greater in patients that did not receive intravenous
thrombolysis before EVT (OR for survival, 6; 95% CI 1.13–31.74). There was no difference
in MAP between groups but a (nonsignificant) trend toward the benefit of MAP < 90 mm
Hg but > 70 mm Hg. Significant hypotension (MAP < 70 mm Hg) is associated with worse
outcomes. This study was limited by its retrospective and observational nature, which
introduces the potential for bias. Hence, the results of this study are hypothesis-generating,
highlighting the need for a larger RCT to clarify the impact of anesthetic agents
on outcomes after EVT under GA.
Intensive Blood Pressure Lowering after Reperfusion Therapy in Acute Ischemic Stroke
BP management in patients with AIS undergoing reperfusion therapy remains an important,
yet unresolved, issue. Failure of autoregulation in the acutely injured brain can
result in significant hyper- or hypoperfusion with the slightest fluctuation in systemic
BP.[16] Several RCTs investigated the efficacy of intensive BP lowering (IBPL) versus standard
BP control (SBPC) post reperfusion therapy. However, discrepancies in their findings
raise doubts about the safety and potential benefits of IBPL after reperfusion therapy.
Chen and Zhu published a systematic review and meta-analysis designed to evaluate
the safety and efficacy of IBPL after reperfusion therapy in AIS.[17] The endpoints of this analysis were functional outcomes (mRS score), symptomatic
ICH, death within 90 days, and recurrent ischemic stroke. Seven eligible studies with
a study population of 4,499 were analyzed. This population comprised of 2,218 patients
in the IBPL group and 2,281 patients in the SBPC group.
Patients undergoing IBPL after EVT exhibited less favorable functional outcomes compared
with those receiving SBPC. Worse mRS scores were seen in the SBP < 140 mm Hg and SBP < 120 mm
Hg subgroups. However, there were no differences between groups in the SBP < 130 mm
Hg subgroup. Though the IBPL group exhibited a lower incidence of ICH in the EVT group,
this did not translate into a long-term functional outcome. No discernible benefits
were observed in other endpoints of this meta-analysis for the EVT subgroup. This
study is limited by the fact that nearly all the study designs were open label, and
only outcome blinding was performed.
Traumatic Brain Injury
Transfusion Strategy in Patients with Traumatic Brain Injury
Anemia in the context of traumatic brain injury (TBI) carries the threat of worsening
cerebral ischemia. Red blood cell transfusion is a common method of treating anemia,
but transfusions can lead to other adverse events. A 1999 trial (TRICC trial) comparing
restrictive versus liberal transfusion strategies in ICU patients showed no mortality
benefit of maintaining high hemoglobin (Hb) levels.[18] However, this trial was not limited to patients with TBI. The Hemoglobin Transfusion
Threshold in Traumatic Brain Injury Optimization (HEMOTION) trial by Turgeon et al
was conducted to compare the effects of a liberal strategy (transfusion trigger Hb
≤ 10.0 g/dL) with a restrictive strategy (transfusion trigger Hb ≤ 7.0 g/dL) on mortality
and long-term functional and patient-centered outcomes in adult patients with moderate-to-severe
TBI.[19] This RCT was performed at 34 centers with 742 patients randomized. The study found
no significant difference in the risk of an unfavorable outcome (Glasgow Outcomes
Scale Extended [GOS-E] ≤ 4) at 6 months (68.4% of patients in the liberal-strategy
group vs. 73.5% in the restrictive-strategy group). The authors also observed no significant
difference in mortality between the two groups (death in ICU 17.1% vs. 15.3%; death
in hospital 23% vs. 21.5%; death at 6 months 26.8% vs. 26.3%). Modern ICU practice
generally favors restrictive transfusion strategies primarily based on the TRICC trial.
The HEMOTION study challenges this approach in critically ill TBI patients. It was
not, however, designed to assess the noninferiority of a more restrictive transfusion
strategy, so the possibility of harm with such a strategy cannot be excluded.
Therapeutic Hypothermia and Traumatic Brain Injury
TBI triggers a cascade of events, such as excitotoxicity, neuroinflammation, apoptosis,
free radical production, seizure activity, and other sequelae, that cause secondary
brain injury. These harmful processes are temperature-dependent and are shown to be
mitigated by therapeutic hypothermia (TH).[20] Previous studies have indicated that TH may be linked to serious complications and
strong evidence on the clinical utility of TH in comparison to normothermia in TBI
is lacking.[21] Martyniuk et al conducted a systematic review and meta-analysis of 32 RCTs with
3,909 patients to synthesize the available clinical data comparing the use of TH with
the use of normothermia in TBI.[21] Pooled analysis revealed a significant benefit of TH on mortality and functional
outcome (RR 0.81, 95% CI 0.68–0.96, I
2 = 41% and RR 0.77; 95% CI 0.67–0.88, I
2 = 68%, respectively). However, subgroup analysis based on risk of bias showed that
only studies with a high risk of bias maintained this benefit. When analyzed by complications,
TH had an increased rate of pneumonia (RR 1.24, 95% CI 1.10–1.40, I
2 = 32%), coagulation abnormalities (RR 1.63, 95% CI 1.09–2.44, I
2 = 55%), and cardiac arrhythmias (RR 1.78, 95% CI 1.05–3.01, I
2 = 21%). When the studies were separated by the risk of bias (low vs. high), there
were no differences in these complications between the two groups. The studies included
in this meta-analysis had substantial heterogeneity, and variable risk of bias, and
some had large confidence intervals, which reduced the quality of evidence. Given
that studies at low risk of bias failed to show any benefit of TH compared with normothermia
in terms of mortality and functional outcome, the authors concluded that this study
does not support the use of TH in severe TBI.
Complications of Intracranial Multimodal Monitoring
Physiological monitors of brain function (for example, tissue oxygenation [PbtO2],
microdialysis, regional cerebral blood flow [CBF], and intracranial electroencephalogram
[EEG] electrodes) are increasingly being used by neurocritical care physicians for
early detection and prevention of secondary insults in patients with acute brain injury
(ABI).[22] Concerns about intracranial multimodal monitoring (iMMM) invasiveness arise due
to limited evidence from retrospective single-center studies, questioning its clinical
significance and safety.[23]
Barrit et al performed a systematic review and meta-analysis aimed at evaluating the
incidence and types of complications related to iMMM.[24] The authors included 22 articles reporting 1,206 patients who underwent 1,434 iMMM
placements. A total of 54 postoperative intracranial hemorrhages (pooled rate of 4%;
95% CI 0–10%; I
2 86%, p < 0.01 [random-effects model]) were reported, along with 46 misplacements (pooled
rate of 6%; 95% CI 1–12%; I
2 78%, p < 0.01) and 16 central nervous system infections (pooled rate of 0.43%; 95% CI 0–2%;
I
2 64%, p < 0.01). Other complications reported included system breaking, dislodgement, intracranial
bone fragments, and pneumocephalus. High-level evidence in the literature was lacking,
and there was significant heterogeneity due to a lack of standardized definitions
in reporting iMMM experiences. The authors attempted to mitigate this by limiting
eligibility criteria. This resulted in them only being able to perform a very constrained
risk factor analysis. Nevertheless, this review underscores the importance of exercising
caution in the application of iMMM, emphasizing the need to improve safety protocols
and patient selection criteria.
Optic Nerve Sheath Diameter and Intracranial Pressure
Elevated ICP or intracranial hypertension (IH) is a critical condition affecting both
pediatric and adult patients, associated with high morbidity and mortality. Accurate
and timely diagnosis is essential to optimize management and improve outcomes. While
invasive techniques remain the gold standard for estimating ICP, optic nerve sheath
diameter (ONSD) measurement via ultrasonography has emerged as a practical, noninvasive
alternative with real-time properties.
A recent systematic review and meta-analysis evaluated the accuracy of ONSD ultrasound
for detecting raised ICP in pediatric patients. Rajendran et al included 25 studies
(1,591 patients and 3,143 ONSD measurements).[25] The analysis revealed a pooled sensitivity of 92% (86–96%) and specificity of 89%
(77–96%), with positive and negative likelihood ratios of 8.6 and 0.08, respectively.
Most studies used a threshold of 4.5 mm or higher for children over 1 year old and
4.0 mm for those under 1 year old to diagnose elevated ICP. Invasive gold standards,
such as external ventricular drain or lumbar puncture, demonstrated sensitivity and
specificity of 94 and 84%, while noninvasive methods (clinical signs and symptoms,
CT, and ONSD ultrasound) achieved 88 and 95%. Studies excluding infants had higher
specificity (98%) compared with those including them (84%). Etiology also impacted
results, with studies focusing on nontraumatic causes yielding higher specificity
(98%) than mixed trauma studies (84%). Limitations of this study included methodological
heterogeneity and publication bias. Despite these limitations, the findings of this
study demonstrate a high diagnostic value of ONSD ultrasonography as a noninvasive
tool for detecting elevated ICP, recognizing it as a reliable diagnostic option for
pediatric ICP monitoring.
Similarly, another systematic review and meta-analysis assessed the accuracy of ONSD
sonography for detecting IH in adult patients with TBI.[26] The meta-analysis included 10 studies involving 512 patients, with pooled sensitivity
and specificity of 85% (95% CI 79–89%) and 88% (95% CI 80–93%), respectively. Positive
and negative likelihood ratios were 7.0 (95% CI 4.1–12.0) and 0.17 (95% CI 0.12–0.25),
with an area under receiver operating curve of 0.91, indicating high diagnostic accuracy.
Although intracranial catheters remain the gold standard for measuring ICP, ONSD represents
a reliable, noninvasive alternative. This study identified an average cutoff value
of 5.8 mm, with optimal ranges between 5.0 and 5.9 mm for elevated ICP, which means
that once ONSD exceeds 5.8 mm, sensitivity and specificity for diagnosis of IH are
high. However, significant variability in cutoff values across all included studies
highlights the need for standardization. In conclusion, ONSD sonography is a noninvasive
and effective tool for detecting IH in TBI patients. Further research is recommended
to standardize protocols and enhance their applicability.
In addition, there were two excellent review articles on the topic of ONSD published
in 2024. Martínez-Palacios et al published a scoping review on using ONSD for ICP
monitoring in TBI.[27] Hirzallah et al published an international consensus statement on ONSD imaging and
measurement focusing on the quality criteria checklist.[28]
Pharmacological Agents
Noradrenaline and Cerebral Blood Flow
Noradrenaline is a vasopressor commonly used to treat hypotension in various clinical
scenarios. The effects of noradrenaline on CBF remain unresolved.
Meng et al published a systematic review with meta-analysis investigating the effects
of noradrenaline on CBF in three distinct populations: healthy individuals, patients
with TBI, and patients suffering from critical illness.[29] Twenty-eight eligible studies were included—8 studies on healthy humans, 9 on patients
with TBI, and 11 on patients with a critical illness. In healthy subjects and noncritical/non-TBI
patients, noradrenaline did not significantly alter CBF velocity (CBFv) (−1.7%, 95%
CI −4.7 to 1.3%) despite a 24.1% (95% CI 19.4–28.7%) increase in MAP. In patients
with TBI, it increased CBFv by 21.5% (95% CI 11.0–32.0%), and MAP by 33.8% (95% CI
14.7–52.9%). In critically ill patients, noradrenaline significantly increased CBFv
(20.0%, 95% CI 9.7–30.3%), along with a 32.4% (95% CI 25.0–39.9%) increase in MAP.
Their analyses indicate preserved cerebral autoregulation in healthy individuals and
patients without critical illness or TBI, while suggesting impaired cerebral autoregulation
in those with TBI or critical illness. Additionally, they demonstrated that the efficacy
of noradrenaline in enhancing CBF is contingent upon not only the status of a patient's
cerebral autoregulation but also the magnitude of the increase in MAP and the patient's
pretreatment BP. Further research investigating outcomes specifically related to the
use of noradrenaline is warranted to further define the critical BP range for individual
patients.
Tranexamic Acid in Neurosurgery
The use of tranexamic acid (TXA) in neurosurgery has expanded in recent years. While
its efficacy in minimizing blood loss and reducing the need for blood transfusion
continues to be an area of active research, concerns regarding its safety profile
have been highlighted. Major concerns include (1) elevated risk of venous thromboembolic
events (VTEs) and (2) the risk for postoperative seizures, attributed to the inhibition
of γ-aminobutyric acid type A receptors and glycine receptors, which increase neuronal
excitability.[30]
Li et al have conducted a randomized, double-blind, placebo-controlled, noninferiority
trial conducted on the safety of a single 20 mg/kg dose of TXA in 600 adult patients
undergoing supratentorial meningioma resection.[31] As part of the anesthetic management, patients were premedicated with midazolam,
followed by sufentanil and propofol boluses for induction. Anesthetic maintenance
was provided through a combined intravenous and inhalation approach, with a propofol
infusion of 3 to 8 mg/kg/h, remifentanil at 0.1 to 0.2 µg/kg/min, and volatile agents
not exceeding 0.5 minimum alveolar concentration. The primary outcome, postoperative
seizures within 7 days, occurred in 4.3% of the TXA group and 3.7% of the placebo
group (normal saline), representing a nonsignificant risk difference of 0.7%, within
the predefined noninferiority margin of 5.5% (p = 0.001). Seizure onset occurred at a median of 2 days, with no differences in subtypes
or recurrence between groups. Secondary outcomes, including VTEs (8.7% in TXA vs.
7% in placebo) and ischemic events (1.3% in TXA vs. 0.3% in placebo), showed no significant
differences. Additionally, nonseizure-related complications, such as hematoma, hydrocephalus,
and infection, as well as postoperative anemia and Hb changes, were comparable across
groups. The study found no significant reductions in intraoperative blood loss or
differences in the use of blood products, hospitalization duration, ICU stays, or
reoperation rates. In summary, a single dose of TXA does not increase the risk of
seizures, or significantly reduce bleeding. Limitations included the single-center
design, reliance on clinical seizure assessment without systematic EEG use, and the
conservative TXA dosing to minimize seizure risk.
On the other hand, a systematic review conducted by Brown et al included 28 studies
(4,461 patients), providing an evaluation of the efficacy and safety of TXA across
a range of neurosurgical indications.[32] Within these studies, six focused specifically on intracranial tumor resections,
such as meningiomas, using a standardized dosing protocol with an intravenous loading
dose of 20 mg/kg over 20 minutes followed by an intraoperative maintenance infusion
at 1 mg/kg/hour. TXA significantly reduced blood loss by an average of 282.48 mL (p < 0.01) and decreased the need for transfusions (OR 0.33, p < 0.01) without increasing the risk of VTEs or postoperative seizures. This reduction
in blood loss and transfusion requirements was consistent across various pathologies
(meningiomas, vestibular schwannomas, gliomas, pituitary adenomas, and pediatric choroid
plexus papillomas). In patients with aSAH, TXA effectively decreased the risk of rebleeding
(RR 0.96, p < 0.01) but did not reduce vasospasm rates (p = 0.27) or improve long-term neurological outcomes. In pediatric craniosynostosis
surgeries, lower dosing protocols (10 mg/kg loading and 5 mg/kg/hour maintenance)
were employed. TXA significantly reduced blood loss by 9.06 mL/kg (p = 0.01) and minimized transfusion requirements (OR 0.34, p = 0.04). Moreover, perioperative complication rates, including VTEs and other adverse
events, did not differ significantly between TXA and control groups (OR 0.47; 95%
CI 0.22–1.01; p > 0.05). Overall, concerns regarding seizure risk attributed to TXA were not significant
and probably mitigated by propofol. Limitations of the review include a lack of standardization
in expected blood loss calculations and potential sampling bias. These findings highlight
TXA's value as a hemostatic agent in neurosurgery, emphasizing the importance of dosing
regimens and patient selection to optimize outcomes.
Dexmedetomidine in Neuroanesthesia and Neurocritical Care
Dexmedetomidine is used widely in neuroanesthesia for its favorable clinical profile,
especially for CS during awake craniotomy. Akavipat et al have published a systematic
review and meta-analysis comparing the effectiveness of dexmedetomidine with propofol-based
sedation for awake craniotomy.[33] A total of 5 RCTs, 3 prospective cohort studies, 11 retrospective cohort studies,
and 3 case series comprising 2,127 patients were analyzed. The outcome measures were
surgical outcome at discharge, the success rate of the surgery, conversion to GA,
and perioperative anesthetic complications. There were no statistically significant
differences in surgical outcomes (RR 1.08, 95% CI 0.94–1.24), conversion to GA (RR
0.45, 95% CI 0.05–3.83), respiratory complications (RR 0.4, 95% CI 0.12–1.27), and
intraoperative nausea and vomiting (RR 0.30, 95% CI 0.08–1.14) between the groups.
However, the intraoperative seizure was higher in the dexmedetomidine group (RR 4.26,
95% CI 1.49–12.16). They found that dexmedetomidine is a safe anesthetic regimen over
propofol alone and a propofol-narcotic-based anesthetic. However, the limitations
suggest larger RCTs are required to prove the findings further.
The use of dexmedetomidine sedation in ICUs is popular as it mimics the natural sleep
state, showing an EEG signal pattern similar to second-stage nonrapid eye movement.
However, there are very few studies on the use of dexmedetomidine sedation in patients
with TBI undergoing mechanical ventilation. Liu et al conducted a retrospective cohort
study examining the sedative practices for patients with moderate to severe TBI undergoing
mechanical ventilation in the neuro-ICU.[34] They examined the association of early dexmedetomidine exposure (within the first
5 days of ICU admission) with clinical outcomes. Among the 19,751 eligible patients,
the study found that propofol (82.7%) was the most commonly used sedative within the
first 2 days of hospitalization followed by benzodiazepines (26.0%), dexmedetomidine
(6.5%), and ketamine (0.9%). With propensity score matching, early dexmedetomidine
exposure was associated with reduced odds of hospital mortality (OR 0.59; 95% CI 0.47–0.74;
p < 0.0001), increased risk for liberation from mechanical ventilation (HR, 1.20; 95%
CI 1.09–1.33; p = 0.0003), and reduced hospital length of stay (HR, 1.11; 95% CI 1.01–1.22; p = 0.033). Exposure to early dexmedetomidine was not associated with higher odds of
discharge to home, vasopressor utilization after the first 2 days of admission, or
increased hospital costs. This study cautiously supports the use of early dexmedetomidine
sedation in the management of patients with TBI and there is a need for further confirmatory
RCTs to better inform optimal sedation for patients with TBI.
Following this, the authors of the above study also conducted two more studies on
the use of dexmedetomidine sedation in patients with moderate to severe TBI. The first
study examined the association of early dexmedetomidine exposure (within the first
5 days of ICU admission) with the primary outcome of the 6-month GOS-E. The secondary
outcomes included the length of hospital stay, hospital mortality, 6-month Disability
Rating Scale (DRS), and 6-month mortality.[35] The study showed that exposure to early dexmedetomidine was not associated with
a favorable GOS-E score (OR 1.30; 95% CI 0.80–2.09). Regarding the secondary outcomes,
patients who were exposed to early dexmedetomidine during admission experienced a
decreased 6-month DRS score (adjusted mean difference [MD], −3.04; 95% CI −5.88 to
−0.21). However, length of hospital stays, the odds of being discharged alive, and
6-month mortality rate were similar between the groups. A post hoc analysis in the
subgroup of the patients who required ICP monitoring found that early dexmedetomidine
exposure was associated with a higher 6-month GOS-E score (OR 2.17; 95% CI 1.24–3.80),
better DRS score (adjusted MD, −5.81; 95% CI −9.38 to −2.25), and reduced length of
hospital stay. In summary, the investigators concluded that early dexmedetomidine
exposure was not associated with improved 6-month functional outcomes in the entire
population, although may have clinical benefit in patients with indications for ICP
monitoring.
The second study investigated the association of early dexmedetomidine exposure with
biomarkers of brain injury in patients with TBI.[36] There has been a growing interest in the utilization of blood-based biomarkers for
their potential in diagnosing and prognosticating TBI. Of particular interest are
biomarkers associated with brain injury including glial fibrillary acidic protein,
ubiquitin C-terminal hydrolase-L1, neuron-specific enolase, S100 calcium-binding protein,
and the inflammatory biomarker C-reactive protein. The authors conducted a retrospective
cohort study using prospective data from the Transforming Clinical Research and Knowledge
in Traumatic Brain Injury Study (TRACK-TB). The outcome measures were blood-based
brain injury biomarker levels obtained on day 3 and days 5 and 14 following injury.
The study showed that there were no differences in the biomarker levels between pre-
(day 1) and postexposure (days 3, 5, 14) to dexmedetomidine. Similarly, there were
no differences between those exposed to dexmedetomidine and those not exposed. Hence,
this study concluded that there is no evidence to suggest that dexmedetomidine exposure
contributes to neuronal injury, supporting its use as a sedative without concern for
harmful effects on the brain.
On the same topic, Hatfield et al have recently published a scoping review on the
safety, efficacy, and clinical outcomes of dexmedetomidine for sedation in patients
with TBI.[37]
Spontaneous ICH is a severe neurological condition associated with high morbidity
and mortality. Elevated BP, a common occurrence after ICH, is an independent predictor
of poor outcomes. Hence, BP control is a critical component of the initial management
of patients with ICH. Antihypertensives are often used as the first line of drugs
for BP control. Dong et al conducted a multicenter, prospective, single-blinded, superiority
RCT to investigate the use of dexmedetomidine in the early BP management in patients
with ICH.[38] The rationale for this approach was that BP control via analgesia, sedation, and
antisympathetic treatment might yield superior outcomes. A total of 338 patients (167
intervention; 171 control) were included on the intention-to-treat basis. The authors
included adult patients with spontaneous ICH and a symptom onset within 24 hours and
with a SBP of 150 mm Hg or greater at least in two consecutive occasions. Patients
in the intervention group received remifentanil combined with dexmedetomidine for
analgesia and sedation, while the control group was treated with urapidil, nicardipine,
or other antihypertensive agents based on guidelines and expert recommendations. The
intervention aimed to reduce SBP to 110 to 140 mm Hg within 1 hour of treatment initiation
and maintain this target during the ICU stay, for up to 7 days. The primary outcome
was the SBP control 1 hour after treatment initiation. Secondary outcomes included
BP variability, hematoma growth, sedation and analgesia scores, neurologic function,
length of ICU stay, number of days on mechanical ventilation, and disability/mortality
rates at 28 and 90 days. Major disability was defined as a mRS score of 3 to 5 at
day 28 and day 90 after randomization. Study results showed that the SBP control rate
at 1 hour was significantly higher in the intervention group when compared with the
control group (62.7% vs. 39.8%; difference 23.2%; OR 2.59; p < 0.001). In addition, the intervention group exhibited reduced BP variability and
better Richmond Agitation-Sedation Scale scores compared with the control group. However,
there were no significant differences between groups regarding other secondary outcome
measures. This trial demonstrated that dexmedetomidine-based BP management achieved
rapid, stable, and effective BP reduction without increasing mortality, outperforming
standard guideline-based treatments. These findings suggest a promising alternative
approach to BP control in ICH patients.
Chronic incisional pain is a common postoperative complication, with the incidence
of chronic postcraniotomy headache ranging from 0 to 65%.[39] Most of this pain (55–79%) is incisional in nature. Opioids remain the primary treatment
for acute postcraniotomy pain, while nonopioid perioperative strategies, such as scalp
nerve blocks and dexmedetomidine, are also utilized. Zeng et al conducted a secondary
analysis of a randomized, double-blind, placebo-controlled trial to evaluate dexmedetomidine's
efficacy in preventing chronic incisional pain.[40] The study included 252 patients, with 128 receiving dexmedetomidine and 124 receiving
placebos. Anesthesia management was similar between both groups. Anesthesia was induced
with propofol, sufentanil, and rocuronium or cisatracurium. Scalp nerve blocks were
done after the induction of anesthesia. Sufentanil boluses (0.1–0.2 μg/kg) were given
to attenuate noxious stimuli responses during surgery. Remifentanil infusion (0.1–0.2
mcg/kg/min) was used intraoperatively to maintain circulatory stability ( ± 20% baseline).
Patient-controlled analgesia with sufentanil was used for postoperative analgesia.
Additionally, the dexmedetomidine group received a 0.6 mcg/kg bolus followed by a
0.4 mcg/kg/h maintenance dose until dural closure, while the placebo group was administered
normal saline. The primary outcome was the incidence of chronic incisional pain at
3 months postcraniotomy. Secondary outcomes included a numeric rating scale (NRS)
pain score, sleep quality, and side effects. Results showed that the incidence of
chronic incisional pain at 3 months was significantly lower in the dexmedetomidine
group compared with the placebo group (23.4% vs. 42.7%; RR 0.55; 95% CI 0.38–0.80;
p = 0.001). Chronic NRS pain scores were also lower in the dexmedetomidine group (p = 0.001). No significant differences were observed in intraoperative adverse events,
postoperative complications, or postanesthesia care unit stay length. The authors
concluded that intraoperative dexmedetomidine infusion significantly reduces the incidence
of chronic incisional pain and improves acute pain scores after elective brain tumor
resections.
Nonsteroidal Anti-Inflammatory Drugs for Postcraniotomy Pain
Postoperative pain after craniotomy can be quite challenging and can lead to negative
psychological, physical, and physiological adverse events. However, opioid use for
pain management can hinder neurological assessments, cause respiratory depression
and increase the risk of opioid dependence. Nonsteroidal anti-inflammatory drugs (NSAIDs)
are effective analgesics with opioid-sparing effects and are part of multimodal pain
management regimens. On the other hand, the increased risk of bleeding with NSAIDs
often restricts the routine use of NSAIDs for postcraniotomy pain. Perez et al conducted
a retrospective study to evaluate the safety of NSAIDs use in the immediate postoperative
period in adults who had craniotomy for tumor resection.[41] The primary outcome was hemorrhage-related complications within 30 days postsurgery.
Secondary outcomes included minimal hemorrhage, acute kidney injury, extracranial
hemorrhage, and oral morphine equivalents within 48 hours. Among patients meeting
inclusion criteria, only 9.6% received NSAIDs. There were no significant differences
in postoperative hemorrhage risks between the NSAID and control groups, except for
higher opioid use in the NSAID group. In their meta-analysis, the estimated RR of
postoperative hematoma requiring reoperation in NSAID users was 0.77 (95% CI 0.46–1.31,
p = 0.32; I
2 = 31%). The study concluded that NSAIDs do not increase hemorrhage risk following
craniotomy for tumor resection and may offer a viable alternative to limit opioid
use. However, the retrospective design, small sample size, and low incidence of reoperation
limit generalizability.
On a similar topic, Harrison et al have published a review article on the pharmacology,
efficacy, and safety of NSAIDs for postcraniotomy pain management in adult and pediatric
patients.[42]
Others
Anesthesia Management of Patients with Chronic Subdural Hematoma
Chronic subdural hematoma (cSDH) is a common neurosurgical condition, particularly
in the elderly population, with an increasing incidence due to aging demographics
and the widespread use of anticoagulants. Surgical interventions are often indicated
in cases of symptomatic or enlarging cSDH. The choice of anesthesia, local anesthesia
(LA) with or without sedation or GA, remains a subject of ongoing debate. Ahn et al
conducted a retrospective study of 383 patients undergoing burr hole craniotomy and
drain insertion for cSDH to analyze the impact of anesthesia type (LA, n = 63 vs. GA, n = 320) on surgical and medical outcomes.[43] Baseline characteristics, including demographics and comorbidities, were similar
between groups, except for a higher proportion of males in the LA group (79.8% vs.
63.4%, p = 0.041). Overall, there were no significant differences in surgical outcomes, such
as postoperative hematoma thickness on CT scan (9.6 mm in the LA group vs. 9.0 mm
in the GA group, p = 0.726), midline shift (p = 0.3), pneumocephalus, ICU stay duration, or recurrence rates (12.7% in LA vs. 11.2%
in GA, p = 0.910). Among medical morbidities, pneumonia was the most prevalent (3.8% in the
GA group vs. 1.6% in the LA group); however, both univariate and multivariate logistic
regression analyses showed that LA did not reduce the incidence of pneumonia (OR 0.41,
p = 0.401). The study concluded that anesthesia type did not influence outcomes. However,
the study's sample size and retrospective design highlight the importance of selecting
anesthesia based on individualized patient profiles.
Extending this debate, a systematic review and meta-analysis compared postoperative
outcomes after cSDH evacuation under LA and GA (12 studies with 1,734 patients).[44] LA demonstrated significant advantages, with lower intraoperative complications
(9.1% in LA vs. 14.7% in GA), fewer postoperative complications (OR 0.38; 95% CI 0.25–0.59;
p < 0.0001), including delirium, pneumonia, dyspnea, and myocardial infarction. No
significant differences were found in the rate of recurrence (5.1% LA vs. 6.9% GA;
p = 0.45) or mortality (3.0% LA vs. 2.3% GA; p = 0.55). Additional advantages found in the LA group include a shorter operative
times (a weighted mean operative time of 46.0 vs. 74.4 minutes for the LA and GA groups,
respectively, with a MD of –29.28 minutes; p < 0.0001) and reduced hospital stays (4.9 vs. 7.6 days for the LA and GA groups,
respectively, with a MD of –1.58 days; p = 0.0002). Despite the methodological strengths of the meta-analysis, limitations
included inconsistent follow-up reporting, variable definitions of complications,
and a lack of blinding in many studies, which may have introduced bias. These findings
suggest that LA is a favorable alternative to GA for elderly patients, offering fewer
complications and faster recovery. In summary, while the choice between LA and GA
for cSDH remains a matter of ongoing research, evidence suggests LA offers advantages
such as fewer complications, shorter operative times, and reduced hospital stays,
without increasing recurrence or mortality.
Bilateral Ultrasound-Guided Erector Spinae Plane Block for Postoperative Analgesia
in Spine Surgery
Severe postoperative pain is common in spine surgeries, particularly spinal fusion
surgery. It negatively impacts long-term outcomes, patient satisfaction, recovery,
and discharge.[45] The use of regional anesthesia techniques, namely, erector spinae plane (ESP) block
for postoperative analgesia after spinal fusion surgeries, has gained popularity in
recent years. Wu et al conducted a systematic review and meta-analysis of 25 RCTs
involving 1,747 patients (873 ESP block group, 874 control group) to evaluate the
efficacy and safety of bilateral ultrasound-guided ESP block.[46] The ESP block group received ropivacaine or bupivacaine blocks, while the control
group received either no block or wound infiltration.
The ESP block group experienced significantly lower pain intensity at 0, 2, 4, 6,
8, 12, 24, and 48 hours compared with controls. Opioid consumption was significantly
reduced (MD = 6.29 mg, 95% CI 8.16–4.41, p < 0.001), and the time to first rescue analgesia was prolonged (MD = 7.51 hours,
95% CI 3.47–11.54, p < 0.001). The ESP block group also had shorter hospital stays (MD = 0.38 days, 95%
CI 0.50–0.26, p < 0.001). While this study highlights ESP block as an effective technique for reducing
pain intensity at rest and during movement for at least 48 hours postsurgery, limitations
include study heterogeneity and small sample sizes. Further large-scale trials are
needed to validate these findings.
Narrative Reviews of Interest
Several excellent review papers focused on topics of particular interest to neuroanesthesiologists
were published over the last year. Carabini et al[47] have published a focused review on perioperative management for complex spinal fusion
surgeries. Ma and Bebawy[48] have published a comprehensive review on anemia and transfusion thresholds in brain-injured
patients. Kartal et al.[49] have published a narrative review focusing on the concept of optimal BP targets
after TBI. On a similar topic, Vu et al[50] published a review article on the physiologic basis, measurement, and clinical implications
of monitoring CBF autoregulation. Battaglini et al[51] published a narrative review on the crosstalk between the nervous system and systemic
organs in ABI. In their review, Mitchell and Flexman[52] have summarized the tools available to measure frailty in the neurosurgical population
and the prevalence of frailty in the spine and intracranial surgical patient cohorts.
They also discussed the current evidence on the relationship between frailty with
postoperative outcomes, and interventions to improve outcomes and future areas of
research. Wiles et al[53] have published a multidisciplinary, multisociety consensus guideline on airway management
for patients with suspected or confirmed cervical spine injury. Frontera et al[54] published a clinical practice guideline for seizure prophylaxis in adults hospitalized
with moderate-severe TBI. Lyons et al[55] published a review on the perioperative management of antithrombotic medications.
Martínez-Palacios et al[56] as a part of the noninvasive ICP monitoring international consensus group, published
a scoping review on the quantitative pupillometry for ICP in TBI. Lele et al[57] published a global survey on the practices in the perioperative management of patients
with aSAH who underwent microsurgical repair of a ruptured intracerebral aneurysm.
Finally, Lewis et al[58] in collaboration with the American Academy of Pediatrics, Child Neurology Society,
and Society for Critical Care Medicine, the American Academy of Neurology published
updated, evidence-informed consensus-based guidelines on pediatric and adult brain
death/death by neurologic criteria determination.
