Non-traumatic subarachnoid hemorrhage (SAH) is a severe disease, mainly caused by the rupture of intracranial aneurysms, accounting for 2–7% of all strokes (1, 2). It is estimated that up to 40% of patients with non-traumatic SAH die in the hospital, resulting in disability and psychological disorders for the patients, and costing a massive amount of money and time (3, 4). Extensive clinical research and maximal treatment have been carried out, but SAH patients still show frustrating clinical outcomes (5). Therefore, there is an urgent need to establish non-invasive and cost-effective detection methods to help identify patients at increased risk of mortality and further optimize treatment.

Creatinine is related to the prognosis of various diseases, such as heart failure, coronary artery disease and cerebral hemorrhage transformation etc. (6–8). Creatinine is an important indicator of kidney function, and the elevation of creatinine levels may indicate kidney impairment (9). Acute kidney injury (AKI) is a common complication in critically ill patients and SAH patients, and its negative impact on outcomes is well known (10). Although the effect of sCr on the neurological function assessment of SAH patients has been described (11), the study’s sample size was small, and there was a lack of data on mortality in critically ill patients.

Therefore, we conducted a retrospective analysis through the MIMIC IV database to describe the association between sCr at admission and 30-day all-cause mortality.

In this study, we analyzed the association between sCr levels and 30-day mortality rate in SAH patients. This study only focused on establishing a predictive model and did not explore causal relationships. Our results indicate that higher sCr is associated with worse 30-day mortality outcomes in SAH patients. Multiple regression analysis demonstrated that after adjusting for other confounding factors, sCr is an independent risk factor for 30-day mortality in SAH patients. The novel line graph based on creatinine levels shows high predictive value.

Creatinine is an assessment indicator of kidney function and is a byproduct of muscle metabolism, primarily derived from the spontaneous non-enzymatic degradation of creatine phosphate (12). Creatine phosphate is stored in muscles, and its degradation produces creatinine, which is then excreted by the kidneys (13). Elevated creatinine levels may indicate impaired kidney function (14).

Research has demonstrated that chronic kidney disease (CKD) has an impact on the mortality rate of patients with aneurysmal subarachnoid hemorrhage (aSAH). One study found that patients with CKD had a higher risk of death during hospitalization for aSAH (15). A systematic review and meta-analysis revealed that CKD affects the mortality rate of patients with subarachnoid hemorrhage (SAH). The study found that ischemic stroke occurred at a higher relative frequency in CKD patients compared to hemorrhagic stroke (78.3 vs. 21.7%). However, as renal function declined, the relative frequency of hemorrhagic stroke gradually increased (16). These research findings suggest that chronic kidney disease may increase the risk of death in patients with aneurysmal subarachnoid hemorrhage. However, diagnosing CKD in patients with acute SAH poses relative difficulties (17). In a clinical setting, obtaining serum creatinine is convenient. We analyzed the first serum creatinine after admission to quickly assess the condition of SAH patients, avoiding the errors associated with repeated measurements and the influence of treatment on post-admission indicators.

Recently, creatinine has been widely used as a prognostic indicator for various critically ill patients. For example, some studies have found that elevated creatinine levels may be associated with the severity of coronary artery disease (6), acute pancreatitis (18), myocardial infarction (19), and the prognosis of symptomatic intracerebral hemorrhage following venous thrombolysis after acute ischemic stroke (8). However, there is limited research on the association between sCr and mortality rates in SAH patients. A previous study involving 369 SAH patients showed that patients with a sCr level ≥ 1.0 mg/dL had a higher likelihood of poorer prognosis (modified Rankin Scale score > 3) compared to SAH patients with sCr levels <1.0 mg/dL (11). These findings align with our study, which demonstrated that patients with sCr level ≥ 0.9 mg/dL had a higher mortality rate compared to those with sCr level < 0.9 mg/dL. Another study involving 66 patients with aSAH found that an early increase in the urea-to-creatinine ratio (UCR) after aneurysmal subarachnoid hemorrhage was independently associated with adverse clinical outcomes (p = 0.026) (20). However, compared to previous studies, our study has several differences. Firstly, we had a larger sample size, focusing on the non-traumatic SAH population in ICU. Secondly, the adjusted variables were also different. We adjusted for several well-known outcome parameters, disease severity, and complications of common critical illnesses.

Nimodipine, a calcium channel blocker, is widely used to reduce the occurrence of cerebral vasospasm and ischemic neurological dysfunction in patients with subarachnoid hemorrhage (SAH). Studies have demonstrated the effectiveness of nimodipine in improving patient prognosis and reducing adverse outcomes (21). Additionally, nimodipine has been shown to decrease the risk of cerebral vasospasm, delayed ischemic neurological dysfunction, and cerebral infarction in SAH patients (22). It is the only effective medication currently available for preventing post-SAH cerebral vasospasm (23). Our study found that the use of nimodipine significantly reduces the 30-day mortality rate in SAH patients with elevated creatinine levels. However, no significant impact was observed in patients with normal creatinine levels. We speculate that this may be due to the slower metabolism of nimodipine in patients with elevated creatinine, resulting in higher drug concentrations and influencing the outcome. Further prospective experiments may be necessary to investigate this hypothesis.

The administration of mannitol has been shown to potentially benefit in reducing intracranial pressure (ICP). Studies have demonstrated the effectiveness of mannitol in lowering ICP and its therapeutic efficacy in patients with subarachnoid hemorrhage (SAH) (24). Particularly, for patients unable to achieve ICP reduction, mannitol treatment has a positive impact on prognosis (25). In summary, mannitol may have a beneficial effect on reducing the mortality rate in SAH patients, although the specific outcomes may vary due to individual differences. Our study found that using mannitol reduces the 30-day mortality risk in patients, regardless of elevated creatinine levels. However, we did not observe a difference in the effectiveness of mannitol between patients with elevated creatinine levels, which suggests that mannitol’s potential renal toxicity does not affect its efficacy. Further research is needed to explore this phenomenon.

It is challenging to elucidate the exact mechanisms through which sCr in non-traumatic SAH patients is closely associated with overall mortality. However, several possible explanations can be proposed. One explanation is that creatinine elevation may be related to coronary artery atherosclerosis. We speculate that it may also be associated with cerebral vasculopathy, leading to increased vessel fragility and susceptibility to damage. Such effect could result in a higher risk of bleeding. Another explanation is that the increase in sCr may be a predictive factor for adverse neurological outcomes due to pre-existing renal dysfunction before SAH. Further research is needed to explore these hypotheses and elucidate the underlying mechanisms.

In summary, the relationship between sCr and 30-day mortality in SAH patients involves specific physiological and metabolic changes that require further research to explore the specific mechanisms. Overall, the factors mentioned above that affect sCr may increase the risk of adverse outcomes in SAH patients, but the exact mechanisms need further investigation.

Firstly, it is a retrospective cohort study with limitations such as potential measurement of missing data and data that may influence the results, such as mFisher grade, Hunt-Hess score, radiological data, and surgical information. Secondly, since creatinine data were only available at baseline upon ICU admission, this study can only establish the correlation between admission creatinine levels and hospital mortality, but not a causal relationship. The statistical methods we employed, such as univariate statistical tests, may lead to the risk of selecting insignificant variables while neglecting significant ones. Future studies may consider utilizing statistical techniques like Lasso regression to reduce statistical errors.

Creatinine can serve as a critical parameter for predicting the prognosis of patients with spontaneous subarachnoid hemorrhage (SAH). The use of a line graph prediction model in conjunction with creatinine can accurately predict in-hospital mortality rates in SAH patients. Applying this prediction model can assist clinicians in assessing the patient’s condition and guide treatment decisions.

The data analyzed in this study were obtained from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database; the following licenses/restrictions apply: to access the files, users must be credentialed users, complete the required training (CITI Data or Specimens Only Research), and sign the data use agreement for the project. Requests to access these datasets should be directed to PhysioNet, https://physionet.org/, DOI: 10.13026/6mm1-ek67.

Ethical approval was not required for the study involving humans in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and the institutional requirements.

YZ: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. HS: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – review & editing. WJ: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – review & editing. LL: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – review & editing. JH: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – review & editing. JM: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. WC: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing.