Clinical and epidemiological profile of patients with neurocritical conditions admitted to intensive care units: a cohort studyABSTRACT
Objective: To describe the epidemiology of patients requiring neurocritical care in intensive care units in Curitiba, Brazil, examine differences based on primary acute neurological diagnoses, and identify predictors of mortality and unfavorable intensive care unit outcomes.
Methods: This was a retrospective cohort study involving patients aged 18 years or older who were admitted to the intensive care units of seven hospitals from January 2017 to December 2022. Patients admitted for primary neurological diagnoses were compared with those admitted for other causes. Cox regression models were used to assess factors associated with mortality and unfavorable outcomes (modified Rankin Scale scores of 4–6) in neurocritical care.
Results: A total of 62,101 patients were included, with 10,884 admitted for neurological reasons. Compared with non-neurological patients, those with neurological diagnoses were significantly older and had lower levels of consciousness upon admission but lower APACHE II and SOFA scores, shorter intensive care unit stays, and lower mortality rates. Despite this, surviving patients admitted with neurological diagnoses experienced greater functional limitations. The leading causes of neurological admission included postoperative monitoring of intracranial surgery (32.6%), ischemic stroke (19%), traumatic brain injury (17%), seizure (7.1%), hemorrhagic stroke (6.5%), subarachnoid hemorrhage (4.5%), encephalopathy (4.2%), spinal cord conditions (3.8%), central nervous system infection (1.8%), neuromuscular diseases (0.8%), and other conditions (2.5%). Older age, use of vasoactive drugs upon admission, creatinine level ≥ 1.5mg/dL, lower level of consciousness within the first 24 hours, and primary neurological diagnoses of ischemic stroke, hemorrhagic stroke, subarachnoid hemorrhage, encephalopathy, and other conditions emerged as independent predictors of an increased hazard ratio of death and an unfavorable intensive care unit outcome.
Conclusion: Patients admitted to intensive care units due to neurological disorders had lower mortality rates but developed higher degrees of functional dependence. Among neurocritically ill patients, those requiring vasoactive drugs upon admission, those with elevated creatinine levels (≥ 1.5mg/dL), and those admitted due to ischemic stroke, hemorrhagic stroke, or subarachnoid hemorrhage had a greater risk of death and unfavorable outcomes.
Keywords:
Critical care; Intensive care unit, Nervous system diseases; Mortality
INTRODUCTION
Neurological disorders contribute to at least 25% of the global disease burden.(1) According to data from the World Health Organization and the 2021 Global Burden of Disease Study, stroke ranks among the three leading causes of death worldwide.(2) In addition to the high mortality burden associated with neurological disorders, the sequelae in surviving patients impact the overall population, affecting both quality of life and functionality while also posing economic challenges.(3,4)
While cerebrovascular diseases are the most recognized neurological disorders causing disability and death, other neurological conditions also impact patients in intensive care units (ICUs) worldwide.(3) Disability and death caused by neurological diseases are increasingly recognized as challenging public health issues globally, and their incidence is predicted to increase in the coming years.(5) In developing countries, these diseases are frequently underrecognized and undertreated.(1)
Severely ill patients with primary neurological diagnoses represent a critical portion of those admitted to ICUs, yet their epidemiological characteristics remain relatively unknown, particularly in low- and middle-income countries. Identifying the regional characteristics of these patients is crucial for prioritizing investments and research areas, improving team training, and improving patient outcomes.(6)
In this context, this study aimed to describe the epidemiology of patients requiring neurocritical care in ICUs in Curitiba, Brazil, examine their differences based on primary acute neurological diagnoses, and identify predictors of mortality and unfavorable ICU outcomes.
METHODS
This study was a retrospective cohort analysis of patients admitted to ICUs in seven hospitals in Curitiba, Brazil, from 2017 to 2022 and assessed the profile of hospitalizations related to neurological disorders.
The study was approved by the Research Ethics Committee (REC) of the Instituto de Neurologia e Cardiologia de Curitiba under opinion number 3.000.353. Informed consent was waived by the REC because of the retrospective nature of the study, the use of anonymized data, and the absence of direct contact with participants. All research procedures were conducted in accordance with the ethical standards of the REC and the Declaration of Helsinki (7th revision, 2013). The study results are reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.
Patient data were obtained from the Centro de Estudos e de Pesquisas em Terapia Intensiva (CEPETI) database. This database is used primarily for clinical care and, secondarily, for research purposes and is maintained daily by intensive care physicians and residents working in the ICUs affiliated with CEPETI.
All ICU admissions of patients over 18 years of age from January 1, 2017, to December 31, 2022, were considered. Duplicate hospitalizations and admissions without data on age, reason for hospitalization, and/or outcome were excluded. Patients admitted due to neurological disorders were categorized into a group labeled "neurological," while those with other reasons for hospitalization were included in a group labeled "non-neurological."
The following variables were collected from all included patients during their ICU stay: age, sex, source of admission, whether the patient received care in the public health sector, reason for admission, need for hemodynamic support with vasoactive drugs (VADs) and invasive ventilatory support at admission, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, serum creatinine level ≥ 1.5mg/dL at ICU admission with an acute increase in the first 24 hours, level of consciousness evaluated using the Glasgow Coma Scale (GCS) at both admission and discharge, level of life-sustaining treatment (LST) limitation on the day of the ICU outcome, length of ICU stay, ICU mortality, and level of functional dependence classified by the intensive care physician on a four-level scale at discharge (for patients who were discharged due to clinical improvement) according to the following categories: independent in all activities, dependent on assistance for complex activities, dependent on assistance for basic activities, and dependent on assistance for all activities.
The level of LST limitation was determined according to the following classification: (A) full ICU care, including cardiopulmonary resuscitation (CPR); (B) full ICU care without CPR; (C) maintenance of LST measures already in place; (D) withdrawal of LST measures when considered futile in the face of a terminal condition.
Based on the ICU outcome, the modified Rankin Scale (mRS) score was estimated for each participant as follows: 0 or 1) independent in all activities; 2) dependent for complex activities; 3) dependent for basic activities; 4 or 5) dependent for all activities; and 6) deceased.
Patients with mRS scores of 4, 5, or 6 were considered to have unfavorable outcomes, whereas those with mRS scores of 0, 1, 2, or 3 were considered to have favorable outcomes.
Patients admitted to the ICU because of neurological diagnoses were compared with those admitted for non-neurological causes in terms of admission characteristics and ICU outcomes.
Patients with neurological disorders were further classified according to the primary reason for ICU admission as follows: postoperative monitoring of intracranial surgery, ischemic stroke, hemorrhagic stroke, subarachnoid hemorrhage (SAH), encephalopathy, seizure, infection, traumatic brain injury (TBI), spinal cord conditions, and other neurological diagnoses. The groups were then compared in terms of their characteristics. The "other neurological diagnoses" group included patients with progressive advanced central nervous system (CNS) neoplasms who received exclusively palliative care. The postoperative intracranial surgery group predominantly consisted of patients who underwent CNS tumor resection and treatment for unruptured cerebral aneurysms.
The characteristics of patients at ICU admission were analyzed considering risk factors for mortality and unfavorable ICU outcomes (mRS scores of 4, 5, or 6).
Statistical analysis
The results for categorical variables are presented as absolute frequencies and percentages. Quantitative variables with normal distributions are presented as mean ± standard deviation, while those that did not exhibit normality are presented as mean and median (interquartile range values). The normality of the quantitative data distribution was assessed using the Kolmogorov–Smirnov test, supplemented by visual analysis of box plots and evaluations of asymmetry and kurtosis.
Associations between two dichotomous variables were evaluated using Fisher's exact test. For nondichotomous categorical variables, associations were assessed using the chi-square test, followed by comparisons of case proportions within each row of the contingency table using the Z test with Bonferroni adjustment.
Comparisons of quantitative variables between two groups were made using Student's t test for independent samples or, if the normality assumption was violated, the nonparametric Mann–Whitney U test. One-way analysis of variance (ANOVA) was used to compare quantitative variables among three or more groups, which was followed by post hoc analysis with the Bonferroni correction if all groups met normality assumptions. Conversely, when normality was not met, the nonparametric Kruskal–Wallis test was applied, followed by Dunn's test with Bonferroni-adjusted significance levels.
Univariable and multivariable Cox regression models were fitted to assess the influence of the following variables on the hazard ratio of death or an unfavorable ICU outcome among neurocritically ill patients: age, sex, primary neurological diagnosis, use of VAD and invasive mechanical ventilation (MV) at admission, creatinine level ≥ 1.5mg/dL, and worst GCS score in the first 24 hours of ICU admission. Variables were selected a priori, following recommendations for observational studies in critically ill patients.(7) Results were expressed as hazard ratios with 95% confidence intervals (95%CIs), and statistical significance was determined using the Wald test. The same analysis was performed stratified by postoperative monitoring of elective surgeries (postoperative monitoring of intracranial surgery) and acute diseases (all other neurological groups).
The level of statistical significance was set at 5%. Data analysis was conducted using IBM SPSS Statistics, version 29.0 (IBM SPSS Inc., Chicago, IL, USA). Missing data were not imputed.
RESULTS
From January 1, 2017, to December 31, 2022, 70,989 hospitalizations were recorded in the participating ICUs. After the selection criteria were applied, 8,888 cases were excluded, resulting in a study sample of 62,101 patients. Among these, 10,884 patients (17.5%) were admitted for neurological reasons (Figure 1).
To characterize neurocritical patients in a general ICU context, where most are treated in Brazil, the neurological group was compared with patients admitted with other diagnoses (non-neurological group). As this is a secondary analysis of the study, the results are presented in the Supplementary Material. Briefly, compared with the non-neurological group, the neurological group had a significantly higher mean age, a lower proportion of admissions through the Unified Health System (Sistema Único de Saúde - SUS), a greater proportion of patients originating from the operating room, and lower proportions of patients requiring VADs at admission and presenting with renal dysfunction. In the first 24 hours in the ICU, patients in the neurological group had a significantly lower GCS score, despite having a significantly lower APACHE II score and shorter ICU stay compared with the non-neurological group. At the time of the outcome, the neurological group had a lower ICU mortality rate; however, survivors had a significantly lower GCS score at discharge (Table 1S - Supplementary Material).
In the multivariate model, compared with the neurological group, the non-neurological group had a 17.4% higher risk of death [HR: 1.174 (95%CI: 1.103 - 1.249) p < 0.001], even when adjusted for VAD use, MV on admission, creatinine level in the first 24 hours, GCS score, age and sex (Table 2S - Supplementary Material). On the other hand, the neurological group had an 8.5% higher risk of adverse outcomes [HR: 1.085 (95%CI: 1.033 - 1.139) p = 0.001] (mRS 4.5 and 6) (Table 3S - Supplementary Material). This finding highlights the greater importance of functional dependence in neurocritical patients, which corroborates the fact that when only ICU survivors were analyzed (n = 52,634), the neurological group had a 48.7% higher risk of total functional dependence [HR: 1.487 (95%CI: 1.365 - 1.619) p < 0.001] (mRS 4 and 5) than the non-neurological group did, even after adjustment for the same variables (Table 4S - Supplementary Material).
The 10,884 patients admitted for neurological reasons were classified into 11 groups based on their primary neurological diagnoses. The largest group (32.7%) consisted of patients in the postoperative period of intracranial surgery, followed by 18.9% with ischemic stroke, 16.9% with TBI, 7.2% with seizures, 6.6% with hemorrhagic stroke, 4.5% with subarachnoid hemorrhage, 4.2% with encephalopathy, 3.8% with spinal cord conditions, 1.8% with CNS infection, 0.8% with neuromuscular disease, and 2.5% with other neurological causes. These groups were then compared in terms of ICU admission characteristics and outcomes (Table 1).
Use of VADs and invasive MV at ICU admission was more frequent among patients admitted for TBI, hemorrhagic stroke, SAH, and CNS infection compared with other neurological diagnoses. Most diagnostic groups exhibited reduced GCS scores in the first 24 hours in the ICU, with TBI, ischemic stroke, hemorrhagic stroke, and SAH exhibiting the lowest levels of consciousness. The 11 diagnostic groups also significantly differed in APACHE II and SOFA scores during the first 24 hours in the ICU, length of ICU stay, mortality rates, and mRS scores (Table 1). Comparisons between the eleven groups and pairwise comparisons are presented in figure 1S (Supplementary Material).
In patients admitted to the ICU for neurological reasons, the influence of age, sex, primary neurological diagnosis, use of VADs and invasive MV at admission, creatinine concentration ≥ 1.5mg/dL, and worst GCS score within the first 24 hours was evaluated concerning the hazard ratio of death and unfavorable ICU outcomes. Univariable results are presented in table 5S (Supplementary Material), while those of the multivariable analyses are shown in table 2.
Hazard ratios adjusted for prognostic factors associated with mortality and unfavorable outcomes among neurocritically ill patients admitted to intensive care units
The group of patients in the postoperative period of intracranial surgery, which had the lowest mortality and unfavorable outcome rates, was used as a reference for comparing the groups admitted for other reasons with respect to both mortality and unfavorable outcomes.
The overall mortality rate was 11.6%, and the unfavorable outcome rate was 19.7%. In the univariable analysis (Table 5S - Supplementary Material), the factors identified as predictors of mortality and an unfavorable outcome included age; use of VAD and MV upon admission; creatinine level ≥ 1.5mg/dL at ICU admission, with an acute increase in the first 24 hours; lower GCS score in the first 24 hours in the ICU; and admission for ischemic stroke, hemorrhagic stroke, SAH, TBI, seizures, encephalopathy, CNS infection, and others, compared with admission for postoperative monitoring of intracranial surgery.
In the adjusted model (Table 2), the following factors remained associated with an increased risk of death and an unfavorable ICU outcome compared with those at admission for postoperative monitoring of intracranial surgery: older age, VAD use upon admission, creatinine level ≥ 1.5mg/dL, lower GCS scores within the first 24 hours in the ICU, and primary neurological diagnoses (including ischemic stroke, hemorrhagic stroke, SAH, encephalopathy, and other neurological diagnoses). Admission due to TBI remained a risk factor for mortality in the adjusted model but lost its association with unfavorable outcomes. The cumulative risk of mortality and unfavorable outcomes for each neurological diagnosis group is displayed in figures 2A and 2B, respectively.
Cumulative hazard ratios for mortality (A) and unfavorable outcomes (B) across neurological diagnoses.
Older age, VAD use upon admission, a creatinine level ≥ 1.5mg/dL, and lower GCS scores within the first 24 hours in the ICU remained risk factors for mortality and unfavorable outcomes in the subgroup of patients with acute neurological diseases (Tables 6S and 7S - Supplementary Material). In the subgroup of patients admitted to the ICU for postoperative monitoring of intracranial surgery, only VAD use and lower GCS scores remained risk factors for both outcomes (Tables 8S and 9S - Supplementary Material).
DISCUSSION
In the present study, the neurological group had a lower mortality rate than the non-neurological group. Patients admitted to ICUs due to neurological conditions often return to society with greater functional dependence, as assessed by functional scales.(8) It is crucial to understand that the greater functional dependence observed in our neurological cohort likely arises from the inherent nature and trajectory of their underlying neurological conditions rather than variations in the quality of critical care provided. Neurological disorders, by their very pathology, often lead to significant long-term functional impairments, irrespective of excellent acute management.
Postoperative monitoring of neurosurgical patients was also identified as the most common reason for ICU admission in the PRINCE Study Part 2, which included patients from 47 countries. Other common neurological diagnoses in the PRINCE Study Part 2 included SAH, hemorrhagic stroke, subdural hematoma, and severe TBI.(9)
In the present study, cerebrovascular events accounted for 30% of all ICU admissions with a primary neurological diagnosis. According to the 2021 Global Burden of Disease, stroke is the third leading cause of death globally and is expected to become the second leading cause of death in the coming years, likely remaining so until 2050.(2)
Similar to the Neurocritical Brazil Study, the present study revealed a predominance of hospitalizations among patients undergoing neurosurgery.(4) These patients generally present with low morbidity and mortality rates, short ICU stays, and low APACHE II scores. However, these findings do not negate the need for critical care during the first postoperative hours for these patients. We recognize that TBI and stroke typically lead to worse outcomes. Therefore, postoperative elective patients were used as a baseline for comparison, as they are the closest to healthy patients in the ICU. Notably, scales used to assess patients admitted to ICUs for all causes may not be applicable to those admitted for neurological reasons, as they may not account for the use of highly complex monitoring devices (such as intracranial pressure monitors and external ventricular shunts) or for parameters related to hypoxia and decreased cerebral blood flow.(10) Furthermore, most Brazilian centers lack adequate monitoring for neurocritically ill patients.(4) Notably, invasive brain oxygenation monitoring in the PRINCE Study Part 2 was performed solely in North America and Europe.(9)
Patients admitted to the ICUs for neurological reasons had a lower mean age than those admitted for non-neurological reasons, with the operating room being the most frequent source of admission for this group. Most patients admitted for neurological reasons were not admitted through the SUS; this trend was driven by an increase in hospitalizations for tumor resections and treatments for unruptured aneurysms, facilitated by advances in imaging techniques and an increase in consultations covered by private health plans.(3) Patients admitted for neurological reasons also had a lower rate of VAD use, less frequent renal dysfunction at admission, and a lower APACHE II score during the first 24 hours. These findings underscore the need to expand severity assessment scales for neurocritically ill patients, focusing on disorders of consciousness, focal deficits, seizures, and other complications that are common in patients with neurological conditions.(11)
The overall mortality rate in the neurological group was 11.6%, comparable to the 12.4% reported in the PRINCE Study Part 2. However, that study highlighted higher and lower mortality rates in Latin America (27%) and Oceania (11%), respectively.(9) In a study conducted by Deuschl et al. in Europe and the European Union, the mortality associated with neurological diseases was 19%, with CNS disorders emerging as the third leading cause of death and disease burden in Europe.(3)
Although the mortality rate in neurocritically ill patients was lower than in controls, patients with diagnoses of TBI, ischemic stroke, hemorrhagic stroke, SAH, encephalopathies, and CNS infections exhibited high mortality rates, particularly those with intracranial bleeding, where mortality reached nearly 30%. These conditions were independent predictors of mortality in neurocritically ill patients, along with the administration of VADs at admission, a serum creatinine level ≥ 1.5mg/dL within the first 24 hours, and a GCS score less than 10.
Additional predictors of unfavorable outcomes included clinical neurological and emergency surgical hospitalization, compared with admission for postoperative monitoring of intracranial surgery, as well as older age, VAD use, renal dysfunction, and reduced level of consciousness—factors also identified as predictors of an unfavorable outcome in a population of neurocritically ill patients in Brazil.(4)
Numerous factors impact neurocritical care and contribute to secondary neurological injury. These factors are closely related to established protocols, team responsiveness, and the prevention of measures known to cause secondary brain injury. Preventive strategies focus on optimizing blood flow and cerebral oxygenation, which depend on the interplay between systemic blood pressure, intracranial pressure, and the regulation of blood gases, such as oxygen and carbon dioxide. Additionally, temperature control and monitoring of hemoglobin, electrolyte, and blood glucose levels play critical roles in determining neurological outcomes.(12) Notably, the protocols used at each hospital included in the present study were not analyzed and likely varied across facilities, which is are important considerations for future studies.
This study has several limitations, including its retrospective design and reliance on a database completed by doctors in each health service, making it susceptible to missing information or errors in data entry. However, cases with identified errors that could not be corrected were excluded, or their variables were not analyzed. Moreover, long-term post-ICU mortality data are unavailable, and this factor can be recognized as a limitation. Another limitation is the high number of patients in the postoperative period of elective surgeries, which may dilute the perceived severity among patients with neurological disorders admitted to the ICUs. Another factor that limits this analysis is that patients came from different centers with different institutional protocols. These protocols varied among health services and were neither standardized nor mandatory, often including variations depending on the local medical definition. While data were collected from seven different hospitals, the focus on patients from a large geographical area (the city of Curitiba) may not accurately represent the neurocritical care landscape of the entire Brazilian population, given the vastness and diversity of care across the country. This is particularly relevant in light of the shortage of intensive care specialists outside of major Brazilian centers. Additionally, specific neurointensive care education remains deficient even in capitals and referral centers in Brazil.(4)
The symptom severity of neurocritically ill patients at admission may have been underestimated, as assessments used scoring systems that are nonspecific for neurointensive care, such as APACHE II and SOFA, with only the GCS—which was originally designed for TBI screening—being considered for evaluating consciousness level. Although this is a limitation, it reflects the global health care reality.(4,9,13)
CONCLUSION
Our findings indicate that among patients with neurological disorders admitted to intensive care units, lower mortality rates were accompanied by a higher degree of functional dependence, particularly regarding dependence on assistance for all activities of daily living and a greater likelihood of becoming completely bedridden.
The clinical progression of patients with neurological disorders can vary widely. Still, some predictors—such as primary neurological diagnoses, vasoactive drug use, mechanical ventilation, renal dysfunction, and altered levels of consciousness upon admission—may be associated with mortality or poorer functional outcomes. Hospitalizations resulting in worse outcomes, such as those due to traumatic brain injury, ischemic stroke, and hemorrhagic stroke, simultaneously present major public health challenges.
Supplementary Materials
Supplementary material 1
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Publisher's note
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Study basis:
Master's Dissertation "Perfil clínico-epidemiológico de pacientes com condições neurocríticas internados em unidades de terapia intensiva em hospitais de Curitiba/PR – Uma coorte histórica" submitted to the Universidade Federal do Paraná, Postgraduate Program in Internal Medicine and Health Sciences. Curitiba, 2025.
AVAILABILITY OF DATA AND MATERIALS
The contents underlying the research text are included in the manuscript.
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Edited by
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Responsible editor:
Ary Serpa Neto https://orcid.org/0000-0003-1520-9387
Publication Dates
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Publication in this collection
12 Dec 2025 -
Date of issue
2025
History
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Received
13 Feb 2025 -
Accepted
19 June 2025
