Introduction

Subarachnoid hemorrhage (SAH), a disease caused by rupture of a cerebral aneurysm, is fatal itself and may lead to severe neurological impairment or death [1,2]. Various complications may occur during the treatment of SAH patients, but cerebral vasospasm (CV), a representative complication, is highly likely to be accompanied by delayed cerebral ischemia (DCI), requiring careful neurological monitoring and treatment [3,4]. CV is a narrowing of the diameter of the cerebral artery, which is reversible and self-limited [5]. CV, a complication of SAH, occurs 3 to 14 days after rupture of the cerebral aneurysm. CV is a narrowing of the cerebral artery diameter, and it is not fatal to the patient alone. However, DCI accompanying CV may have fatal consequences for the patient [6,7]. The incidence of CV confirmed on angiography of computed tomography (CT) is approximately 50% to 70% in SAH patients with ruptured cerebral aneurysms [8,9]. Not all patients with angiographically occurring CV develop symptoms. Approximately 30% to 40% of these patients develop symptoms due to DCI, which may result in fatal neurological consequences such as loss of consciousness, hemiplegia, and speech disorders [4,10,11]. Rapid and accurate screening of CV is necessary to avoid DCI, a serious complication of SAH that causes significant symptoms in patients. The most important point in the treatment of neurologically critically ill patients is the symptoms of patients. In cases of SAH, the symptoms of patients are identified through intensive care in the neurological intensive care unit. When DCI occurs due to CV, mood changes such as irritability, confusion, and lethargy may occur, and other symptoms such as headache, focal weakness, speech impairment, and decreased consciousness may also occur [8,12]. When these symptoms occur, CV should be diagnosed and ruled out by using various diagnostic methods. Among the various methods, the most commonly used methods are brain CT angiography (CTA) and transcranial Doppler (TCD). Brain CTA has limitations due to side effects from radiation exposure and the use of contrast agents [9]. In particular, TCD is a good diagnostic tool for early detection of CV in various aspects [13]. First of all, in terms of usage, it has advantages for both patients and practitioners. Its noninvasiveness, measurability at the bedside without moving the patient, and its low cost enable daily measurements (3 to 14 days) during the CV risk period [14]. When the mean blood flow velocity of the middle cerebral artery (MCA) is measured and the measured value is 120 cm/sec or higher, CV may be suspected diagnostically. If CV is suspected after the TCD test, additional brain CTA may be performed to confirm CV through imaging studies. TCD is known to be an accurate diagnostic tool with high sensitivity and specificity [15]. This study investigates the actual patient group of the institution to find out the correlation between TCD and CV and whether it is valuable to perform the test on a daily basis.

Methods

Ethical statements: This study was approved by the Institutional Review Board (IRB) of Kosin Medical Center (IRB No. KUGH IRB 2024-08-021). Written informed consent was waived.

1. Patient

The data was collected from a single institution for a total of 2 years from January 2022 to December 2023. A study was conducted for 2 years targeting non-traumatic SAH patients, and a total of 152 patients were enrolled. This study selected cerebral aneurysm rupture-related SAH patients, and those who did not undergo TCD testing were excluded. Their condition was poor when they first visited the emergency room, and they died within 3 days of admission. A total of 143 patients were enrolled in the study, and this study was conducted as a retrospective study.

2. Clinical management

At the time of admission, the Hunt-Hess grade was recorded through a neurological examination of the patient before surgical or interventional procedures, and the modified-Fisher grade was also recorded through an initial brain CT. All patients underwent emergency conventional surgical treatment (surgical clipping, trapping and bypass) or endovascular intervention (coiling, stent assisted coiling, trapping) and were treated in the neurological intensive care unit. All patients also received brain CT and CTA prior to treatment. All patients received continuous neuromonitoring in the neurological intensive care unit. Neurological examinations and urine output were checked on an hourly basis, and vital signs were monitored continuously. The euvolemic principle was applied in the treatment of patients, and normal systolic blood pressure was used as the reference point for care. Immediately after admission to the intensive care unit, oral nimodipine 60 mg was administered every 4 hours. When the patients showed high intracranial pressure, decompressive craniotomy, external ventricular drainage, or lumbar drainage was additionally performed. TCD tests were performed on a daily basis from the 3rd day to the 14th day. If the patients did not show neurological changes, showed TCD flow velocity lower than 120 cm/sec, or did not show significant changes in TCD flow velocity within a day (differences of more than 50 cm/sec), brain CT+CTA was performed on the 7th and 14th days. In cases of radiological CV with no difference in neurological symptoms, induced hypertensive treatment was used. In cases of DCI onset accompanied by CV, brain CT was performed to identify low-density lesions and confirm the diagnosis. If the patient had neurological symptoms along with CV, the patient received active treatment as soon as possible. Trans-femoral cerebral angiography (TFCA) was performed as an emergency procedure through a trans-femoral approach in the angiography room to determine the degree of spasm in the major cerebral vessels. Afterwards, nimodipine was diluted with normal saline and injected through a microcatheter. After confirming the degree of recovery of vessel diameter, hypervolemic and induced-hypertension treatment was performed in the neurological intensive care unit.

3. Diagnostic techniques

TCD tests performed daily were performed at the bed side by trained nurses. The device used for the Doppler ultrasound examination at our institution was PMD 150 digital transcranial Doppler system (Spencer Technologies). The figures were checked through each temporal lobe on both sides. TCD figures were measured daily and stored in a computer database in the neurological intensive care unit. When a TCD flow velocity figure was 120 cm/s or higher or showed a difference of 50 cm/sec or higher within 24 hours, the system reported it directly to the attending physician. The results were obtained by measuring the temporal bone area, which is the thinnest area, and measuring both the left and right sides. Blood flow velocity was measured in both the MCA and the anterior cerebral artery using a 2-MHz portable hand-transducer probe.

4. Statistical analysis

Statistical analysis was performed using the SPSS 25.0 for windows (IBM Corp.). The correlation between TCD measurements and Hunt-Hess grade and modified Fisher grade was statistically evaluated using the Mann-Whitney U-test. The chi-square and Fisher exact tests were used for categorical variables according to their characteristics. The results of TCD were presented as percentages with 95% confidence intervals (CI). The criterion for indicating statistical significance was p-value <0.05 in all analyses.

Results

This retrospective study collected data over 2 years from January 2022 to December 2023, and a total of 143 patients was included in the criteria. The mean age was 59.28±13.27 years. Females accounted for 83 patients, or 58% of total patients. The most common location of the cerebral aneurysm causing SAH was the anterior communicating artery, accounting for 49 cases (34.3%) of the total patients, followed by the bifurcation of the MCA and the posterior communicating artery. When the cerebral artery location was largely divided into anterior and posterior, aneurysm ruptures in the anterior circulation accounted for 128 cases (89.5%). In this study, cerebral aneurysms located in the posterior circulation were located in the posterior inferior cerebellar artery, basilar artery, superior cerebellar artery, and vertebral artery (Table 1). Hunt-Hess grade and modified Fisher grade data were also collected through neurological examination and brain CT at the time of admission of SAH patients (Table 2). In cases of Hunt-Hess grade, the neurological examination results of the patients showed that grade Ⅲ, a drowsy level of consciousness, and grade Ⅳ, a stupor level of consciousness, respectively accounted for 35% and 37% of the total patients, accounting for 72% of the total patients. In cases of modified-Fisher grade, grade Ⅲ, in which SAH volume was 1 mm or more on CT and intraventricular hemorrhage was present, accounted for 42% (60 patients), the largest group. The criteria for treatment selection in SAH patients were the location and size of the cerebral aneurysm, the age of patients, and the overall condition, and were selected between conventional surgical methods and endovascular intervention. In cases where the volume of intracerebral hemorrhage was large or hydrocephalus was present that intracranial pressure was high, conventional surgical methods enabling decompressive craniotomy were selected (Table 3). In brain CTA taken from 3rd to 14th day, CV occurred in 84 patients (58.7%) compared to the initial CTA, and in cases of TCD, it was confirmed that the flow velocity value of the MCA was 120 cm/sec or higher, which was confirmed in 86 patients (60.1% of the total patients) (Table 4). The Hunt-Hess grade records related to the level of consciousness of the patients at the time of ictus were checked to confirm the correlation between CV and grade, and a statistically significant correlation was confirmed (Table 5). Analysis of the correlation between modified-Fisher grade and CV, which are related to the amount of bleeding and the presence or absence of intraventricular hemorrhage on brain CT, also obtained statistically significant values (Table 6). A validation study was conducted to confirm the accuracy of initial screening using TCD in patients suspected of CV. In patients diagnosed with CV on TCD, vasospasm was confirmed on actual CTA in 92.7% of cases, and in patients with normal TCD values, CTA was also normal in 89.1% of cases, showing a significantly high probability of accuracy and obtaining statistically significant values (Table 7). The utility of TCD screening as a diagnostic tool prior to confirmation of CV by CTA was excellent that the sensitivity of 0.93 (95% CI, 0.87–0.97), specificity of 0.89 (95% CI, 0.81–0.96), positive predictive value of 0.91 (95% CI, 0.85–0.96), negative predictive value of 0.91 (95% CI, 0.84–0.95). According to the results of this study, TCD showed high numerical values in all areas.

Discussion

When SAH occurs due to rupture of a cerebral aneurysm, patients have high morbidity and mortality. SAH patients may develop various complications, such as rebleeding, cerebral infarction, and hydrocephalus, and one of the most fatal complications is CV [16,17]. CV stands for transient cerebral vasoconstriction and may occur from 3 to 14 days after ictus. However, this constriction of cerebral blood vessels itself does not cause harm to the patient. CV may cause and result in cerebral ischemia, and this DCI may bring critically fatal consequences to the patient. Patients may experience a variety of symptoms, including headache, decreased consciousness, hemiparesis, aphasia, and dysarthria, and if DCI progresses further, it may lead to death. DCI, a complication that occurs as a result of CV, requires rapid screening and appropriate treatment [18-20]. Accurate and rapid diagnosis and appropriate treatment have a positive effect on the prognosis of SAH patients [21]. The purpose of this retrospective study was to investigate the diagnostic value of appropriate and early TCD monitoring. In this study, females were slightly more prevalent (58%) in the SAH patient group, the location of the cerebral aneurysm was much more common in the anterior circulation (89.5%), and the most common location was the anterior communicating aneurysm (34.3%). These results were not significantly different from other previously conducted papers [21,22]. The results of the research showed that the Hunt-Hess grade, which indicates the level of consciousness of SAH patients, and the modified-Fisher grade, which indicates the degree of hemorrhage in brain CT, were statistically significant predictors of CV. Oxyhemoglobin in blood clots derived from SAH is a key role in CV. It is known that methemoglobin and superoxide anion radicals and lipid peroxidation caused by oxyhemoglobin lead to damage of endothelial cells and smooth muscle cells, resulting in decreased endothelial nitro oxide and increased endothelin-1, which in turn causes cerebral vessel spasm [23-25]. When SAH occurs due to rupture of a cerebral aneurysm, patients show high morbidity and mortality. SAH patients may develop various complications, such as rebleeding, cerebral infarction, and hydrocephalus, and one of the most fatal complications is CV [16,17]. CV stands for transient cerebral vasoconstriction, and it may occur from 3 to 14 days after ictus. However, this constriction of cerebral blood vessels in itself does not cause harm to the patient. CV may cause and result in cerebral ischemia, and this DCI may have highly fatal consequences for the patient. Patients may experience a variety of symptoms, including headache, decreased consciousness, hemiparesis, aphasia, and dysarthria, and further progress of DCI may lead to death. DCI is a complication that occurs as a result of CV, and it requires rapid screening and appropriate treatment [18-20]. Accurate and rapid diagnosis and appropriate treatment have a positive effect on the prognosis of SAH patients [21].

When a patient presents with neurological changes due to CV, CTA of brain, and TFCA become the gold standard for diagnosis. However, brain CTA has several disadvantages. First, there is the risk of having to move the patient from the intensive care unit to the CT room, and it also may involve radiation exposure and complications from contrast agents. Although TFCA is the most reliable and accurate method for diagnosing CV, it has more dangerous disadvantages than CTA. TFCA is an invasive procedure, and infection, vascular dissection, cerebral infarction may occur during the procedure [26-29]. From this perspective, TCD is considered to be a highly effective diagnostic tool for predictive diagnosis of CV. Like several previous studies [5-7,21,22], this study confirms and highlights these advantages of TCD.

TCD was effectively used for the early detection of CV and had a diagnostic value in predicting the onset of DCI caused by CV. TCD also reduces the risk to patients, saves time until CV diagnosis, and ultimately reduces complications. TCD, which measures the mean blood flow velocity of the MCA using the thinnest part of the temporal bone as a window, is known to have high sensitivity and specificity around 90% [14,15,30].

In the current study, the sensitivity and specificity of TCD were significant high at 93% and 89%, respectively, and such a result ultimately led to the rapid diagnosis of CV and prompt and appropriate treatment of DCI patients. Several previous studies have reported that the mean blood flow velocity of the MCA measured by TCD shows a correlation in patients with asymptomatic CV [7,18], symptomatic CV [16], and DCI [19]. The crucial point is the utility of TCD in patients with symptomatic CV and DCI. In patients with SAH caused by cerebral aneurysm rupture, the occurrence rate of DCI ranges from 10% to 20% [3-5,7]. Patients with ischemic damage show a high probability of developing neurological deficit, and TCD is an excellent diagnostic tool for the early detection of such patients. Patients with DCI caused by CV require brain CTA, medical treatment, and TFCA followed by intra-arterial vasodilator administration, balloon angioplasty, or angioplasty using an intravascular stent. As TCD is easily available at the bedside on a daily basis, it saves time and cost for these systems. Despite these various advantages, there are also disadvantages to the TCD technique. Depending on the skill level of each individual performing the test, there may be differences in the test results, and in cases where the temporal bone is thick, measurement may be difficult.

This study has several limitations. First, it is a retrospective cross-sectional study. Second, this study was conducted in a single center, so the generalizability of the results cannot be guaranteed. Multicenter studies are needed to apply the results to a larger population.

Brain CTA or TFCA is essential for confirming CV. As shown in Table 7, CTA identified CV in 92.7% of cases when the TCD result was 120 cm/sec or higher. The results of this study imply that it is reasonable to use mean blood flow velocity of MCA via TCD for monitoring CV based on reliable data with statistical confidence. These high predictive diagnostic results of TCD provide a rapid treatment protocol for CV patients with symptoms and contribute to saving the time for an appropriate treatment. TCD does not require movement of the critically ill patient, and this effective, accurate, and inexpensive test should be used on a daily basis for 3 to 14 days in cases of CV risk.

Article information

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

Funding

None.

Author contributions

All the work was done by JHP.

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