Clinicoradiological and Biochemical Predictors of Mortality in Hospitalized Patients of Spontaneous Intracerebral Hemorrhage

Abstract Background  Intracerebral hemorrhage (ICH) is a cerebrovascular insult leading to bleeding within the brain parenchyma. It is associated with high rate of mortality and morbidity. The main objective of our study was to study in-hospital predictors of mortality in patients with spontaneous ICH managed medically. Methods  This was a single-center prospective study and patients of ICH meeting the inclusion criteria were recruited from March 2019 to December 2020. Demographic data were collected and brain imaging was done. Each patient was observed for outcome with either discharge or death. Results  Total 202 patients of ICH were included in the study. Mean age of the patients was 58.46 ± 11.6 years (26–95 years), which included 75.25% males. Most common location of ICH was gangliocapsular (42.08%) followed by thalamus (37.13%). Overall mortality was 35.60% ( n  = 72). On univariate analysis, predictors of mortality were higher age, low Glasgow coma scale (GCS) score, intraventricular extension, volume of hematoma, raised ICH score, leucocytosis, raised creatinine, hypernatremia, and ventilatory support. Need for ventilatory support, raised serum creatinine, and low GCS was found to be independent predictor of mortality on multivariate analysis. Conclusion  Our study showed that about one-third of ICH patient died during in-hospital management. Mechanical ventilation requirement, low GCS, and raised creatinine were found to be independent predictors of mortality in our study.


Introduction
Stroke is one of the leading causes of disability and mortality worldwide. Stroke is responsible for11.6% of all deaths worldwide and is the second most common cause of death following ischemic heart disease. 1 Intracerebral hemorrhage (ICH) refers to bleeding within brain parenchyma and defined by its location within the brain parenchyma. ICH occurs in 10 to 15% of all stroke cases with a very high rate of mortality and morbidity requiring prolonged hospitalization. In developed countries, the incidence of hypertensive ICH has reduced with the improvement in blood pressure control. However, in developing countries like India, the burden of ICH has not decreased. 1 The outcome of ICH depends on various factors such as hematoma volume, location, and extension to ventricles. 2 Between 35 and 52% of people die within 30 days, while 20% of survivors recover fully functionally within 6 months. 3 Approximately half of Keywords ► intracerebral hemorrhage ► ICH ► stroke ► mortality ► spontaneous ► predictors Abstract Background Intracerebral hemorrhage (ICH) is a cerebrovascular insult leading to bleeding within the brain parenchyma. It is associated with high rate of mortality and morbidity. The main objective of our study was to study in-hospital predictors of mortality in patients with spontaneous ICH managed medically. Methods This was a single-center prospective study and patients of ICH meeting the inclusion criteria were recruited from March 2019 to December 2020. Demographic data were collected and brain imaging was done. Each patient was observed for outcome with either discharge or death. Results Total 202 patients of ICH were included in the study. Mean age of the patients was 58.46 AE 11.6 years (26-95 years), which included 75.25% males. Most common location of ICH was gangliocapsular (42.08%) followed by thalamus (37.13%). Overall mortality was 35.60% (n ¼ 72). On univariate analysis, predictors of mortality were higher age, low Glasgow coma scale (GCS) score, intraventricular extension, volume of hematoma, raised ICH score, leucocytosis, raised creatinine, hypernatremia, and ventilatory support. Need for ventilatory support, raised serum creatinine, and low GCS was found to be independent predictor of mortality on multivariate analysis. Conclusion Our study showed that about one-third of ICH patient died during inhospital management. Mechanical ventilation requirement, low GCS, and raised creatinine were found to be independent predictors of mortality in our study.
Article published online: 2023-04-24 this mortality occurs within the first 24 hours that shows critical importance of early and effective treatment in the emergency department.
There are only few studies published from India predicting factors affecting mortality in hospitalized patients with ICH. 4 The main objective of our study was to describe clinicodemographic profile of ICH patients managed medically and determine the factors affecting mortality in the hospitalized patients of ICH in our tertiary care hospital.

Materials and Methods
This was a single-center prospective observational study done on patients of ICH between March 2019 and December 2020. The study was approved by the institutional ethics committee. Written informed consent was obtained from all patients or their guardians for participation in the study. All the patients with the sudden onset acute neurological deficit of vascular origin with neuroimaging suggestive of ICH were included in the study. The following group of patients were excluded from the study: (1) Patients having tumoral and traumatic bleeding, that is, contusion/epidural hemorrhage/subdural hemorrhage; (2) ICH due to secondary causes like anticoagulant therapy/post-thrombolytic/vascular malformation rupture; (3) patients or attendant not giving consent for participation in the study; (4) patients who underwent neurosurgical intervention for ICH.
All the admitted patients were evaluated in detail including demographic details such as age, sex, and address along with clinical data such as handedness, vascular risk factors (hypertension, diabetes, previous stroke), addictions (smoking, tobacco chewing, alcohol), and presenting complaints (contralateral weakness, slurring of speech, altered sensorium, vomiting, headache, and convulsion). Detailed neurological examination was done at the time of admission. The level of consciousness was graded with Glasgow Coma scale (GCS). Patients underwent investigations such as complete hemogram, serum biochemistry (liver function test, kidney function test), prothrombin time/International normalized ratio, electrocardiogram, ultrasound abdomen, two-dimensional echocardiography, and brain imaging. Brain imaging included noncontrast computed tomography brain. Neuroimaging was assessed for location (gangliocapsular, thalamus, cortical, cerebellar, brainstem, intraventricular) and volume of ICH with its secondary complications like mass effect, midline shift, and ventricular extension. The volume of hematoma was calculated by ABC/2 method and ICH scoring was done by using ICH scoring system given by Hemphill et al. 2 All patients received antiedema measures like mannitol or hypertonic saline, intravenous fluids, and management of hypertension and diabetes mellitus. All the patients were managed conservatively without any neurosurgical intervention. Patients shifted to intensive care unit (ICU) who need intensive monitoring or ventilatory support. Repeat CT was done for patients in ICU for worsening sensorium or new neurological deficit. Patients were followed up during the course of hospitalization with the outcome being either discharge or death of the patient.
Mortality predictors were assessed in relation to demographic (age, sex), clinical (GCS, requirement of ventilatory support), biochemical (leukocyte count, serum creatinine and serum sodium), and radiological (location of bleeding, intraventricular extension (IVE), hematoma volume) parameters. Leucocytosis was considered if total cell count was above 11 Â 10 3 /mm 3 , raised serum creatinine more than 1.5 mg/dL, and hypernatremia more than 145 mmol/L. Comparison was made for these parameters among survived and deceased.
Statistical analyses were done with Statistical Package for Social Sciences, SPSS (Version 20.0, SPSS Inc.). Categorical variable between deceased and survived was compared using the chi-squared test (or Fisher's exact test) and continuous variable was compared using independent t-test or Mann-Whitney U test. Predictors of mortality were assessed using a univariate binary logistic regression analysis followed by a multivariate analysis adjusting the covariates with a p-value of less than 0.05 in the univariate analysis. A variable having an exact two-tailed p-value of less than 0.05 in statistics was considered significant.

Baseline Characteristics
In this study, 202 patients were included fulfilling inclusion criteria. Mean age of study subjects was 58.46 AE 11.6 years. Majority of the patients were males (i.e., 75.25%). Around two-thirds (64.85%) of the patients were tobacco chewer. The most common presentation was contralateral weakness (81.18%) followed by slurring of speech (39.6%) and altered sensorium (39.6%). Diabetes was present in 13.86% of cases, while hypertension in 83.17% cases. GCS score was less than 8 in 29.7% patients at the time of admission.

Discussion
ICH is the most devastating form of stroke causing severe disability among survivors. It is associated with high mortality as observed in previous studies. Accurate prediction of ICH outcome in the emergency department is important for making decisions about the judicious use of scarce resources. 5 In present study, mean age and gender distribution of patients with ICH is comparable to previous studies from India by Hegde et al, 4 Bhatia et al, 6 and Modi et al. 7 ICH is reported to be more common in advancing age and male sex. 8 Bahou 9 and Namani et al 10 reported the commonest clinical symptom as limb weakness similar to our study. Headache and altered sensorium were present in more than one-third patients of ICH in our study. Kumar et al 11 reported that most common symptoms were limb weakness followed by altered sensorium and headache, while Ojha et al 12 and Hegde et al 4 reported that the common presenting symptoms were headache and loss of consciousness.
Most common location of ICH was gangliocapsular followed closely by thalamus comparable to a study by Narayan et al. 13 Our findings were in line with study of Bhatia et al 6 where each of lobar bleeding, brainstem bleeding, and cerebellar bleeding were less than 10%. The mean volume of ICH was comparable to mean volume of bleeding in a study by Hegde et al. 4 Age showed significant association with mortality as patients who died had significantly higher age similar to the study by Hegde et al 4 and Kumar et al, 11 who reported that higher age holds significant association with mortality, while Ojha et al 12 and Bhatia at al 6 reported that the mean age of patients who succumbed and those who survived was comparable. However, gender showed no association with mortality in this study similar to study by Bhatia et al 6 that showed gender distribution was comparable in those who died and were alive.
Mortality was significantly higher in patients with low GCS in the present study. Our study findings were in line with the study by Hegde et al, 8 who reported that GCS score of less than 8 was present in significantly more patients in deceased versus alive. Other studies from India also have reported similar findings, with Bhatia et al 6 and Namani et al 10 reporting a fatality of 72.9 and 100%, respectively, with poor GCS on admission. Safatli et al 15 also reported that in a multivariate analysis, low GCS was a significant predictor for the 30-day mortality.
Hemphill et al, 2 Cheung and Zou, 16  Leucocytosis is associated with increased mortality in ICH patients similar to the results of meta-analysis done by Yu et al 18 as it might point toward septicemia. Our study showed that raised creatinine level and hypernatremia was significantly associated with mortality. However, in the study by Bhatia et al, 6 as compared with those who survived versus those who died had no difference in the biochemical parameters. Deranged creatinine was found to be associated with mortality in study by Rhoney et al. 19 Our study showed similar findings, as patients who developed acute renal dysfunction with ICH or hypertension related to chronic kidney disease were associated with raised creatinine. Hypernatremia at the time of discharge is found to be associated with mortality in ICH patients. 20 Mortality was significantly higher in patients requiring ventilatory support as compared with patients not requiring ventilatory support similar to the findings corroborated in study by Bhatia et al 6 as need for ventilatory support indicates raised intracranial pressure or any pulmonary infection.
This study excluded the spontaneous ICH patients with neurosurgical intervention and role of such intervention on mortality. Further studies might be required to study the impact of neurosurgical intervention on mortality and discharged patients could have been followed up for further complications and 30-day mortality. Also, this study has not studied vascular risk factors like hypertension, diabetes mellitus, and dyslipidemia in relation to mortality. These are the major limitations of this study.

Conclusion
The present study revealed mortality in about one-third patient of ICH. On univariate analysis, higher age, low GCS score, IVE, higher volume of bleeding, leucocytosis, increased creatinine, hypernatremia, and ventilatory support were the predictors of mortality. Low GCS score, raised creatinine, and ventilatory support were the independent predictor of mortality on multivariate analysis. This indicates the importance of clinical, biochemical, and radiological parameters at admission in effectively prognosticating about the mortality.