J Cerebrovasc Endovasc Neurosurg > Volume 27(4); 2025 > Article
Tunthanathip, Duangsoithong, and Sae-Heng: Prognosis of subarachnoid hemorrhage determined by intracranial pressure thresholds

Abstract

Objective

Subarachnoid hemorrhage (SAH) is a severe neurological condition often associated with elevated intracranial pressure (ICP), which can impact patient outcomes. The present study aimed to evaluate the prognostic significance of ICP thresholds in predicting prognosis in SAH patients.

Methods

A retrospective cohort study was conducted, including patients diagnosed with SAH who underwent ventriculostomy between January 2019 and December 2024. Prognostic factors were estimated from various clinical-radiographic characteristics and ICP using the Cox regression model. Additional analyses were performed to evaluate the relationship between ICP thresholds and hazard ratio by dose-response analysis.

Results

A total of 110 SAH patients were included in the study. The analysis demonstrated a significant association between elevated ICP and poor outcomes (Hazard ratio (HR) 1.06, 95% CI 1.03-1.09). In multivariable analysis, ICP value was significantly associated with prognosis when the model was adjusted with pupillary light reflex (HR 1.04, 95% CI 1.01-1.08). In addition, SAH patients were divided into two groups based on the ICP cutoff value of 24 mmHg. Consequently, the group with ICP values of 24 mmHg or higher was strongly associated with poor prognosis (p-value of log-rank test=0.01).

Conclusions

Our study demonstrates that elevated ICP, particularly beyond the threshold of 24 mmHg, is strongly associated with poor outcomes in SAH patients. These findings support the inclusion of ICP thresholds in prognostic assessment and underscore the need for vigilant ICP monitoring and early intervention in the neurocritical care setting.

INTRODUCTION

Subarachnoid hemorrhage (SAH) is a critical cerebrovascular event caused by bleeding into the subarachnoid space, frequently resulting from ruptured intracranial aneurysms [10,15,17]. Mortality caused by SAH has been reported in a range of 20%-50% from prior studies [3,9]. SAH not only provides immediate life-threatening risks, but it also causes long-term functional deficits in survivors. Greebe et al. examined long-term functional outcomes using the modified Ranking Scale (mRS) and reported that 55.7% of SAH patients improved their mRS after a 4-month follow-up [5]. Therefore, A prognostic evaluation in SAH patients is required to develop appropriate therapeutic strategies.
Intracranial pressure (ICP) is one of the key factors that determines a patient’s outcome after the accumulation of blood between the arachnoid and pia mater. However, the optimal ICP thresholds for SAH patients have been debated from the review of the literature. Marbacher et al. investigated the pathogenesis of brain injury following SAH in animal experiments and found that SAH induced a rapid increase in ICP, which corresponded to decreased cerebral perfusion pressure (CPP) and regional cerebral blood flow [12]. Consequently, sustained high ICP correlates with poor neurological outcomes [1]. Zoerle et al. found that SAH patients with ICP greater than 20 mmHg had a significantly higher mortality rate than patients with ICP 20 mmHg or less [28]. According to Heuer et al., the following is a negative correlation between an increase in ICP and a favorable outcome. Favorable 6-month outcomes were observed in 71.9% of patients with ICP less than 20 mmHg, 63.5% of patients with ICP between 20 and 50 mmHg, and 33.3% of patients with ICP greater than 50 mmHg [6].
Though neurocritical care has advanced, the optimal ICP criteria for thresholds for guiding personalized treatment will be better neurological outcomes and prognosis. The review of the literature has not clearly defined the optimal ICP cutoffs for prognostic prediction [26]. The present study aimed to determine the prognostic value of different ICP thresholds in SAH patients. By identifying critical ICP cutoffs, our findings may help improve clinical decision-making and patient management strategies.

MATERIALS AND METHODS

Study designs and study population

Following the Ethics Committee and Institutional Review Board of the Faculty of Medicine approval, the retrospective cohort analysis proceeded with a review of the electronic medical records of SAH patients who were admitted and underwent ventriculostomy at a tertiary hospital between January 2019 and December 2024. Patients were included if they had confirmed SAH via cranial computed tomography and had ICP monitoring before aneurysmal treatment. At our institution, the cause of SAH was diagnosed using computed tomography angiography or digital subtraction cerebral angiography. Once aneurysmal SAH was confirmed, patients were urgently evaluated for definitive treatment. The choice of aneurysmal treatment between surgical clipping and endovascular coiling was determined based on multiple factors, including the location and morphology of the aneurysm, patient stability, and the neurosurgeon’s preference. Ventriculostomy was typically performed, particularly in cases of acute hydrocephalus, and intraoperative ICP values were recorded at the time of catheter insertion. Exclusion criteria included traumatic SAH and incomplete medical records.
Patient demographic data, Hunt-Hess grade scale, World Federation of Neurosurgical Societies (WFNS) grade scale, neuroimaging findings, modified Fisher grading, and treatment modalities were collected. Intraoperative ICP value was recorded during ventriculostomy with the centimeter of water unit (cmH2O). Therefore, ICP with cmH2O unit was converted to a millimeter of mercury unit (mmHg) by converting 1 cmH2O to 0.736 mmHg before analysis [19].
The follow-up data was acquired through March 31, 2025. The period of survival was estimated from the date of surgery to the latest follow-up or death date. The last clinical state at the last follow-up was censor (still alive) or mortality. Patient visits to outpatient clinics served as the main source of follow-up information. Additionally, patients (or their caretakers) who were unable to visit the hospital were interviewed over the phone.

Statistical analysis

Descriptive statistics were utilized to determine the demographics of the study population. Specifically, the continuous variables were displayed by the mean and standard deviation (SD), while the categorical variables were reported as percentages.
Cox regression analysis was used to determine prognostic factors. Univariate analysis was used to screen all variables, and variables with a p-value of less than 0.1 were identified as candidate variables. Consequently, multivariable analysis was used to examine a number of prognostic variables. In detail, backward stepwise production was performed, and the final prediction model was chosen using the lowest Akaike information criterion (AIC). Therefore, the Schoenfeld residuals were then examined against the assumption of the Cox proportional hazards model. Furthermore, the predictive performance of the final model was performed using Harrell’s concordance index (c-index).
To further illustrate the relationship between ICP thresholds and hazard ratio (HR), a dose-response curve was created. The HR and corresponding 95% confidence intervals (CI) were estimated to quantify the relative risk of adverse outcomes across different ICP levels. The threshold ICP level at which HR equals 1 was identified to indicate a potential risk transition point. Additionally, survival curves were constructed using the Kaplan-Meier method. The log-rank test was used to evaluate the p-value for survival when comparing dichotomous features between groups. The statistical analysis was performed using the R version 4.3.3 software.

Ethical considerations

The Human Research Ethics Committee approved the present study (REC 68-017-10-1). Because this study was a retrospective review, the patient’s informed consent was not required. However, patient identification numbers were encoded before analysis.

RESULTS

As a result, Table 1 presents the clinical features of the 110 patients with SAH. There was a female predominance at 66.4%, with a mean age of 60.59 (±16.42) years. Hypertension, dyslipidemia, diabetes mellitus, and ischemic heart disease were identified in 46.4%, 23.6%, 10.9%, and 6.4% of the patients, respectively. Headache and motor weakness were common symptoms in 57.3% and 57.3% of cases, respectively. Furthermore, seizure was found in 15.5% of the present cohort. In terms of clinical severity grading scales, 47.3% of cases were Hunt and Hess grade IV, with 18.2% being grade V. In WFNS grade, 76.3% of the present cohort were grade IV-V.
Modified Fisher grade IV is the most common imaging severity in the present study, accounting for 70.0% of cases, whereas obliterated basal cistern was observed in 18.2% of cases. According to the cerebral angiogram, the ruptured aneurysm of the anterior cerebral circulation was 51.8%, while 48.2% of SAH cases had the ruptured aneurysm from the posterior circulation. Based on treatment modalities, 65.5% of patients underwent endovascular coiling, and surgical clipping was performed in 34.5% of cases. Furthermore, all patients underwent ventriculostomy and the average intraoperative ICP was 17.90 (+8.47) mmHg.
The mean follow-up time was 15.81 (+24.01) months and the maximum follow-up period was 106 months. As a result, 1-year, 2-year, and 5-year survival probabilities were 0.62 (95% CI 0.53-0.73), 0.59 (95% CI 0.49-0.71), and 0.54 (95% CI 0.42-0.70), respectively. Additionally, the median overall survival time was determined; however, the estimated median survival was not achieved from the entire dataset and the overall survival curve is demonstrated in Fig. 1.
From univariate analysis, the candidate variables with a p-value of 0.1 or less included Hunt and Hess grade, WFNS grade, pupillary light reflex, and ICP value. Hence, the final prediction model that had the lowest AIC value comprised pupillary light reflex, and ICP value, as shown in Table 2. The p-value of the global Schoenfeld test was 0.73 and the final model did not violate the proportional hazards assumption. Furthermore, Harrell’s c-index was 0.728 for estimating the predictive performance.
As a result, HR with 95% confidence intervals was computed across various ICP levels, and a dose-response curve was constructed, as illustrated in Fig. 2. The ICP value of 24.34 mmHg was the potential risk transition point from the HR of one. The ICP at the potential risk transition point is positively related to mortality. In addition, dose-response curves were created according to the pupillary light reflex group for subgroup analysis. As shown in Fig. 3, only the fixed-both-eyes group showed the potential risk transition point at the ICP of 25.75 mmHg, while other groups did not. Therefore, SAH patients were dichotomized into two groups: the group with an ICP value of less than 24 mmHg and the group with an ICP value of 24 mmHg or higher. The group of an ICP value of 24 mmHg or higher was significantly associated with poor prognosis (p-value of log-rank test=0.01), as demonstrated in Fig. 4.

DISCUSSION

This present study identified ICP as the potential prognostic factor in patients with SAH, emphasizing its independent association with mortality and poor prognosis. Our findings are consistent with previous studies underscoring the detrimental impact of elevated ICP in patients with hemorrhagic stroke. Zhang et al. [26] revealed that the crucial ICP threshold for patients with spontaneous intracerebral hemorrhage was 16.5 mmHg, whereas we identified a threshold ICP value of 24 mmHg as a potential transition point beyond which the hazard of death increases significantly. The dose-response analysis supports the hypothesis that higher ICP levels are associated with worse outcomes. Kaplan-Meier analysis and multivariate Cox regression confirmed that patients with ICP 24 mmHg or more had notably lower survival probabilities.
Interestingly, the subgroup analysis based on pupillary light reflex revealed a distinct risk transition point (25.75 mmHg) only in patients with fixed pupils, implying that the prognostic value of ICP may be modified by neurological examination findings. From prior studies, several independent prognostic factors have been reported, such as increasing age, high WFNS grade, intraventricular hemorrhage, intracerebral hematoma, and vasospasm [13,16,27]. Additionally, pupillary light reflex has been reported as a predictor in prior studies. Mader et al. [11] created and validated the prognostic score systems based on pupil status and found areas under the receiver operating characteristic curves (AUROC) of the scoring systems ranged from 0.775 to 0.841, while Dengler et al. reported AUROC ranging from 0.75 to 0.82 using a clinical-radiographic scoring system with pupil status for prognostication [4]. The predictive performance of our work is consistent with that of previous studies. While various clinical-radiographic factors remain pivotal in outcome prediction, ICP presents a dynamic and quantifiable parameter that can be continuously monitored and actively managed. Therefore, external validation should be performed in the future for generalizability [18,20,23].
To the authors’ knowledge, although prior studies have explored the prognostic implications of elevated ICP in SAH, dose-response analysis of ICP thresholds remains relatively uncommon [24-26]. The present study contributes to the growing body of evidence by applying a hazard-based dose-response approach to identify a specific ICP cutoff associated with poor outcomes. However, the authors recognized that there are some limitations to the present study.
In the present study, ICP value was collected and analyzed by intraoperative ICP measurement at the time of ventriculostomy. While the precise interval from symptom onset to ICP measurement was not recorded for all patients due to the retrospective nature of the study, we recognized its potential importance. Therefore, average ICP should be used in future prospective investigations.
As a single-center retrospective study, our results were susceptible to selection bias and might not be generalizable to broader populations [7,8]. To reduce bias, multicenter research should be performed in the future to increase the size of the study population and provide new data for updating the prediction model [13,14,21,22]. Furthermore, future research should investigate patient-specific ICP targets, and combining ICP with multimodal monitoring (e.g., CPP, brain tissue oxygenation) could enhance individualized care strategies.
Currently, various prediction tools have been employed for prognostication in SAH patients, including traditional clinical nomograms and more advanced machine learning-based models. These tools aim to improve the accuracy of outcome prediction by integrating multiple clinical and radiological parameters [27-29]. However, a comprehensive comparison of their predictive performance, usability, and real-world applicability remains limited [30]. Future research should focus on systematically evaluating these methodologies to determine their relative strengths, limitations, and potential for integration into clinical workflows, ultimately enhancing individualized patient care and decision-making [2,31].
In clinical implication, these findings may serve as a foundation for developing and refining prediction tools through the Plan-Do-Check-Act (PDCA) cycle [32,33]. Specifically, the Plan phase involves defining an ICP threshold (e.g., 24 mmHg) for closer monitoring and timely intervention. The Do phase integrates the threshold into healthcare workflows, such as alarm systems or escalation protocols. During the Check phase, patient outcomes and intervention effectiveness are assessed using audits or quality indicators. Finally, the Act phase applies the findings to refine prognostic models and improve clinical guidelines. In this context, the PDCA cycle provides continual quality improvement, ensuring that ICP monitoring techniques are evidence-based and adaptive to future data [34].

CONCLUSIONS

Our study demonstrates that elevated ICP, particularly beyond the threshold of 24 mmHg, is strongly associated with poor outcomes in SAH patients. These findings support the inclusion of ICP thresholds in prognostic assessment and underscore the need for vigilant ICP monitoring and early intervention in the neurocritical care setting.

NOTES

Declarations

All procedures performed in the study that involved studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee or both and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards (REC 68-017-10-1).

Author contributions

TT and RD conceived the study and designed the method. SH supervised the completion of the data collection. TT and RD undertook the recruitment of participating centers and patients and managed the data, including quality control. TT provided statistical advice on the study design and analyzed the data, while TT drafted the manuscript, and all authors contributed substantially to its revision. TT takes responsibility for the paper as a whole.

Disclosure

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Fig. 1.
Kaplan-Meier method of overall prognosis.
jcen-2025-e2025-04-003f1.jpg
Fig. 2.
The dose-response curve between intracranial pressure and hazard ratio using total data. ICP, intracranial pressure.
jcen-2025-e2025-04-003f2.jpg
Fig. 3.
The dose-response curve between intracranial pressure and hazard ratio by pupillary light reflex. ICP, intracranial pressure; BE, both eyes; OE, one eye.
jcen-2025-e2025-04-003f3.jpg
Fig. 4.
Kaplan-Meier method by ICP groups. ICP, intracranial pressure; gr, group.
jcen-2025-e2025-04-003f4.jpg
Table 1.
Clinical characteristics (N=110)
Factor N (%)
Age group (year)
 <15 1 (0.9)
 15-60 51 (46.4)
 >60 58 (52.7)
Mean age (year) 60.59 (16.42)
Gender
 Male 37 (33.6)
 Female 73 (66.4)
Underlying disease
 Hypertension 51 (46.4)
 Dyslipidemia 26 (23.6)
 Diabetes Mellitus 12 (10.9)
 Ischemic heart disease 7 (6.4)
 Renal failure 6 (5.5)
 Liver disease 3 (2.7)
Headache 63 (57.3)
Seizure 17 (15.5)
Motor weakness 63 (57.3)
Glasgow Coma Scale score
 13-15 26 (23.6)
 9-12 30 (27.3)
 3-8 54 (49.1)
Hunt and Hess grade
 I 0 (0)
 II 24 (21.8)
 III 14 (12.7)
 IV 52 (47.3)
 V 20 (18.2)
World Federation of Neurosurgical Societies (WFNS) grade
 I 16 (14.5)
 II 8 (7.3)
 III 2 (1.8)
 IV 57 (51.8)
 V 27 (24.5)
Pupillary light reflex
 Fixed BE 12 (10.9)
 React OE 8 (7.3)
 React BE 90 (81.3)
Mean size of co-existing intracerebral hematoma (cm) (SD) 0.80 (1.63)
Mean midline shift (mm) (SD) 0.43 (1.38)
Obliterated basal cistern 20 (18.2)
Modified Fisher grade
 1 7 (6.4)
 2 5 (4.5)
 3 21 (19.1)
 4 77 (70.0)
Type of aneurysm
 Ruptured aneurysm of anterior cerebral circulation 57 (51.8)
 Ruptured aneurysm of posterior cerebral circulation 53 (48.2)
Treatment modality
 Surgical clipping 38 (34.5)
 Endovascular coiling 72 (65.5)
Mean intracranial pressure (mmHg) 17.90 (8.47)

SD, standard deviation; BE, both eyes; OE, one eye.

Table 2.
Factor associated with prognosis using univariate analysis
Factor
Univariate analysis
Multivariable analysis
Hazard ratio (95% CI) p-value Hazard ratio (95% CI) p-value
Age group (year)
 <15 Ref
 15-60 0.21 (0.03-1.63) 0.13
 >60 0.25 (0.03-1.89) 0.17
Mean age (year) 0.99 (0.97-1.01) 0.89
Gender
 Male Ref
 Female 0.84 (0.44-1.62) 0.60
Underlying disease
 Diabetes Mellitus* 0.79 (0.28-2.24) 0.66
 Hypertension* 1.11 (0.59-2.09) 0.73
 Dyslipidemia* 0.75 (0.35-1.64) 0.46
 Liver disease* 1.92 (0.46-7.99) 0.41
 Ischemic heart disease* 0.36 (0.05-2.62) 0.23
 Renal failure* 1.68 (0.52-5.48) 0.41
Headache 0.61 (0.32-1.14) 0.12
Seizure 1.40 (0.62-3.19) 0.43
Motor weakness 1.52 (0.78-2.95) 0.21
Glasgow Coma Scale score
 13-15 Ref
 9-12 1.28 (0.49-3.38) 0.61
 3-8 1.87 (0.80-4.41) 0.15
Hunt and Hess grade
 II Ref
 III 1.96 (0.57-6.76) 0.29
 IV 2.23 (0.84-5.98) 0.11
 V 3.12 (1.04-9.36) 0.04
World Federation of Neurosurgical Societies (WFNS) grade
 I Ref
 II 0.97 (0.18-5.30) 0.97
 III 2.88 (0.32-25.83) 0.34
 IV 1.43 (0.49-4.22) 0.51
 V 2.82 (0.91-8.70) 0.07
Pupillary light reflex
 Fixed BE Ref Ref
 React OE 0.17 (0.05-0.63) 0.008 0.27 (0.07-1.03) 0.05
 React BE 0.13 (0.06-0.27) <0.001 0.16 (0.07-0.35) <0.001
Mean size of co-existing intracerebral hematoma (cm) (SD) 1.07 (0.90-1.27) 0.45
Mean midline shift (mm) (SD) 1.15 (0.95-1.40) 0.19
Obliterated basal cistern 1.47 (0.70-3.10) 0.32
Modified fisher scale grade
 1 Ref
 2 0.28 (0.03-2.49) 0.25
 3 0.65 (0.20-2.13) 0.48
 4 0.46 (0.16-1.34) 0.15
Type of aneurysm
 Aneurysm of anterior circulation Ref
 Aneurysm of posterior circulation 1.40 (0.74-2.63) 0.29
Treatment modality
 Surgical clipping Ref
 Endovascular coiling 1.17 (0.59-2.32) 0.64
Intracranial pressure (mmHg) 1.06 (1.03-1.09) <0.001 1.04 (1.01-1.08) 0.004

* Data show only “yes group” while reference groups (no group) are hidden.

SD, standard deviation; BE, both eyes; OE, one eye.

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