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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 13  |  Issue : 1  |  Page : 23-28

Predictors of outcome in spontaneous intracerebral hemorrhage with special reference to hyponatremia


Department of Medicine, VMMC and SJH Hospital, New Delhi, India

Date of Submission17-Jul-2021
Date of Decision20-May-2021
Date of Acceptance21-Sep-2021
Date of Web Publication24-Jan-2022

Correspondence Address:
Dr. Tulika Porwal
3059, Sector A, Pocket B and C, Vasant Kunj, New Delhi - 110 070
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/INJMS.INJMS_78_21

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  Abstract 


Objective: The study was done to find the various clinical, biochemical and radiological predictors of outcome in spontaneous intracerebral hemorrhage (SICH) patients and to assess the role of hyponatremia as a predictor of in-hospital mortality. Materials and Methods: This was a hospital based prospective observational study conducted in the department of Medicine, VMMC and Safdarjang Hospital, New Delhi, India on 75 adults (>18 years of age, both male and female) presenting with SICH. Various parameters comprising demographic, clinical, laboratory, and radiological variables along with stroke severity were assessed and studied as predictors of in-hospital outcome, i.e., mortality and disability at the time of discharge as assessed by modified Rankin's Scale (mRS) in 75 SICH patients presenting to the emergency department. Furthermore, the role of hyponatremia as a predictor of in-hospital mortality was studied. Results: Out of 75 patients enrolled in the study, 40% (n = 30) of the patients died in the hospital and 60% (n = 45) were discharged. Out of the discharged category, 80% (n = 36) had mild disability with mRS 1–3 and 20% (n = 9) had moderate-to-severe disability with mRS 4-5. National Institute of Health Stroke Scale (NIHSS) at the time of hospitalization was found to be the significant independent predictor of in-hospital mortality and higher mRS score at discharge. Furthermore, Glasgow Coma Scale (GCS) ≤4 and NIHSS >12 were significantly associated with in-hospital mortality. Hyponatremia was found in 44% (n = 33) of the patients at the time of hospitalization and out of them sodium level got corrected in 15.15% (n = 5). Out of the 42 normonatremic patients 31% (n = 13) developed hyponatremia in subsequent days during hospitalization. No association was found between hyponatremia and in-hospital mortality. Conclusion: Our study highlights the fact that SICH is associated with high in-hospital mortality. NIHSS score at the time of hospitalization is an independent predictor of in-hospital mortality and disability at discharge. Furthermore, GCS ≤4 and NIHSS >12 are significantly associated with in-hospital mortality. Although hyponatremia is a common occurrence in patients with SICH, our study failed to show association between hyponatremia and in-hospital mortality.

Keywords: Hyponatremia, modified Rankin scale, mortality, spontaneous intracerebral hemorrhage


How to cite this article:
Porwal T, Mohanty S. Predictors of outcome in spontaneous intracerebral hemorrhage with special reference to hyponatremia. Indian J Med Spec 2022;13:23-8

How to cite this URL:
Porwal T, Mohanty S. Predictors of outcome in spontaneous intracerebral hemorrhage with special reference to hyponatremia. Indian J Med Spec [serial online] 2022 [cited 2022 Oct 2];13:23-8. Available from: http://www.ijms.in/text.asp?2022/13/1/23/336429




  Introduction Top


Intracerebral hemorrhage (ICH) accounts for 10%–20% of all strokes.[1] and is the deadliest, most disabling and least treatable form among all strokes. Around 32%–50% of patients die within 1st month and only 20% are independent at 6 months.[2],[3] A number of studies have investigated the relationship of various clinical and radiological factors with poor outcome. Furthermore, several prognostic models based on clinical, laboratory, and neuroimaging parameters have been proposed as predictors of mortality in spontaneous ICH (SICH), however, only the original ICH score by Hemphil et al.[4] has been validated in geographically distant and socioculturally distinct population so far. Out of the various parameters, Glasgow Coma Scale score (GCS score) and hematoma volume are the most consistent outcome predictors. Less consistent factors include age, presence and degree of brainstem hemorrhage, and presence and degree of hydrocephalus.

Hyponatremia is the most frequently encountered electrolyte disturbance in patients in critical care including neurointensive patients such as postoperative neurosurgical patients, traumatic brain injury and subarachnoid hemorrhage and has been associated with increased mortality and morbidity. In a recent study by Kuramatsu et al.[5] involving SICH patients, hyponatremia was identified as an independent predictor for in hospital mortality. In this study, prevalence of hyponatremia on hospital admission was 15.6%. Normonatremia was achieved and maintained in all hyponatremic patients in <48 h. However, correction of hyponatremia did not seem to compensate its influence on mortality which warrants future research.

The present study was designed to determine predictors of in-hospital outcome in SICH patients with emphasis on the role of hyponatremia which is a potentially reversible condition.


  Materials and Methods Top


This was a hospital-based prospective observational study conducted over a 2 year period in the department of Medicine, VMMC and Safdarjung Hospital, New Delhi. Study was conducted on 75 adults (>18 years of age, both male and female) presenting with SICH to the emergency department and after fulfilling inclusion and exclusion criteria. Patients presenting after 24 h of onset of neurological symptoms, ICH due to trauma, tumor, AV malformation, hemorrhagic transformation of cerebral infarct and ICH due to platelet count <50,000/ml or INR >1.4, post thrombolytic therapy or with anticoagulant therapy were excluded. The study protocol was approved by the institution's Ethics Committee, and written informed consent was obtained from the patients or their relatives. Data were collected from the patients in a standardized data collection form. Patients were subjected to detailed history and thorough general physical and systemic examination. The following details were collected, i.e., age, sex, history of diabetes, hypertension, dyslipidemia, drug abuse, and use of any drugs such as diuretics, antiplatelet, anticoagulants, smoking, alcohol abuse, GCS, National Institute of Health Stroke Scale (NIHSS), and ICH score. All the patients were subjected to investigations like complete blood count, liver function test, kidney function test, electrolytes, serum osmolality, coagulation profile, lipid profile, and noncontrast computerized tomography (NCCT) of Head. Serum Sodium was estimated at the time of hospitalization and then on daily basis till discharge/death. Sodium calculation was done on a Hitachi 902 Roche auto-analyser by ion selective electrode. Hyponatremia was defined as serum sodium <135 mEq/l. All the patients were followed till their discharge/death. Functional disability at the time of discharge was assessed by modified Rankin's Scale (mRS).

The NCCT head findings were interpreted by a radiologist and following features were recorded, i.e location-supratentorial/infratentorial, and size of hematoma, intraventricular extension, midline shift in mm and associated hydrocephalus. Volume of the hemorrhage was calculated by the formula ABC/2, where A is the greatest diameter, B is the diameter perpendicular to A, and C is the approximate number of the CT slice with hemorrhage multiplied by the slice thickness.

Statistical analysis

Quantitative variables were compared using unpaired t-test/Mann–Whitney test and qualitative variables were correlated using Chi-square test/Fisher's exact test. Receiver operating characteristics (ROC) were used to find out cut off point, sensitivity, and specificity of GCS, Midline shift, NIHSS and size of hematoma for predicting mortality. Univariate and multivariate logistic regression analysis was used to find out predictors of mortality and linear regression was used to find out predictors of mRS score. P < 0.05 was considered statistically significant and analysis was done using SPSS version 21.0.


  Results Top


A total of 75 patients of SICH were enrolled, out of which 40% (n = 30) died in the hospital and 60% (n = 45) were discharged with disability. Patients' characteristics according to in-hospital outcome are as per [Table 1]. The mean age of the patients in the death category was 57.4 ± 14.44 years as compared to 52.38 ± 14.01 years in the discharged category. Majority of patients i.e. 80% (n = 24) in the death category were males. However, no significant association was found between age, sex, and in-hospital mortality. Out of total study population, 33% (n = 20) were smokers and 26.67% (n = 20) were consuming alcohol. Both smoking and alcohol consumption were found to be significantly associated with in-hospital mortality (P = 0.003 and P = 0.033 respectively). Furthermore, about 42.67% (n = 32) and 8% (n = 6) of the study population were hypertensive and diabetic, respectively. However, mean systolic and diastolic pressure, mean arterial pressure, and mean random blood sugar were not significantly different in both the categories. A higher stroke severity at admission as measured by GCS and NIHSS scores and higher ICH score was observed to be significant risk factors for in-hospital mortality.
Table 1: Distribution of the patients according to the in-hospital outcome

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Out of various biochemical parameters studied, patients who died had higher mean triglyceride level as compared to those who were discharged (P = 0.001). Hyponatremia was found in 44% (n = 33) of study population at the time of hospitalization and out of them, sodium level got corrected in 15.15% (n = 5).Out of 42 normonatremic patients 31% (n = 13) developed hyponatremia in subsequent days during hospitalization. There was no significant difference in the distribution of hyponatremia among the death versus discharge category (P = 0.924).

Size of hematoma as well as midline shift were significantly higher in the death category as compared to discharged patients (P = 0.003 and P = 0.013, respectively). However, location of hematoma, i.e., infratentorial versus supratentorial and intraventricular extension was not risk factors for mortality. None of the patients in the discharged category were put on mechanical ventilation as compared to the 73.33% (n = 22) in the death category (P < 0.0005). Furthermore, patients who died had shorter hospital stay (P < 0.0005).

ROC [Table 2] was used to find out cut-off with optimum sensitivity and specificity of GCS, NIHSS, size of hematoma, and midline shift for predicting in-hospital mortality. Out of the four parameters, GCS score ≤4 was found to be the best predictor of mortality.
Table 2: The characterstics of receiver operating characteristics curves

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Predictors of in-hospital mortality

Univariate logistic regression analysis showed that smoking, alcohol, mechanical ventilation, increase in NIHSS score, cholesterol, triglyceride, size of the hematoma, midline shift and decrease in GCS, and length of hospital stay significantly increase the risk of mortality. However, in multivariate analysis [Table 3], NIHSS was the significant independent predictor of mortality after adjusting for confounding factors. GCS ≤4 and NIHSS >12 were significantly associated with the in-hospital mortality.
Table 3: Multivariate logistic regression analysis for predicting mortality

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Predictors of modified Rankin's Scale score

Univariate linear regression analysis showed that Smoking, mechanical ventilation, increase in ICH score, NIHSS score, triglyceride, size of the hematoma, midline shift, decrease in GCS, and the length of hospital stay significantly increases the risk of higher mRS score. However, on multivariate linear regression analysis [Table 4], NIHSS score was found to be the significant independent predictor of mRS score.
Table 4: Multivariate linear regression analysis with Modified Rankin's Scale score as a predictor of disability

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  Discussion Top


ICH still remains a grave medical emergency with high mortality and morbidity. In spite of improvement in outcomes in ischemic stroke, outcomes in patients with ICH still remains poor with no specific medical treatment. Furthermore, surgical interventions in SICH have yielded either negative or inconclusive results[6],[7],[8] except one recent study in young adults showing lower mortality following surgical evacuation.[9] Therefore, early recognition of high-risk patients is critical for effective management.

In our study, various clinical, biochemical, and radiological parameters were analyzed as risk factors for in-hospital mortality. The mortality rate in the present study was about 40%, which is quite comparable to a recent Indian study by Bhatia et al.[6] which reported in-hospital mortality from ICH of about 32.7%. The 30-day mortality from ICH ranges from 35% to 52% with one half of these deaths occurring within the first 2 days.[10],[11],[12] Furthermore, our study observed association between smoking, alcohol consumption, and risk of in-hospital mortality. According to an earlier study by Juvela et al.,[13] the amount of alcohol consumed within 1 week before ICH seemed to be an independent factor determining outcome and hence alcohol was considered to be a modifiable prognostic factor. Although numerous mechanisms exist by which heavy use of alcohol may predispose to stroke, those particularly relevant to ICH raised blood pressure and it's inhibitory effect on platelet function. Our study failed to show association between comorbidities such as hypertension, diabetes mellitus, mean arterial BP, and mean random blood sugar at the time of presentation with in-hospital mortality which is in concurrence with the study by Bhatia et al.[6]

An increased stroke severity at presentation as assessed by GCS and NIHSS scores was observed in patients with in-hospital mortality. However, only higher NIHSS score at presentation was found to be the significant independent predictor of disability. Furthermore, GCS ≤4 and NIHSS >12 were significantly associated with in-hospital mortality. Various earlier studies have found a similar association between high initial stroke severity and mortality.[4],[6],[9],[14] GCS ≤8 was found to be an independent predictor of mortality in the study by Bhatia et al.[6] Two other studies[4],[14] have shown low GCS at presentation to be independent predictor of 30-day mortality. Furthermore, in a study by Koivunen et al.[9] higher NIHSS score was found to be an independent predictor of 3-month mortality.

Furthermore till date, few hematological and biochemical parameters such as anaemia.[15] serum cholesterol[16] and hyponatremia have been found to be associated with poor outcome in SICH. As hyponatremia is a potentially reversible condition, we assessed the role of hyponatremia as predictor of in-hospital mortality. About 44% study population presented with hyponatremia at the time of hospitalization and out of them, only in 15%, hyponatremia got corrected. Furthermore, about 31% of the normonatremic patients developed hyponatremia later during the hospital stay. It is not clear whether hyponatremia is due to associated comorbidities, polypharmacy, or due to associated brain injury resulting from ICH.

Pathological mechanisms that link hyponatremia to outcome in neurointensive care patients include development of cerebral edema, seizure, and delayed cerebral infarction. In these patients, hyponatremia may be caused by syndrome of inappropriate antidiuretic hormone secretion and cerebral salt wasting syndrome. Our study failed to show association between hyponatremia and in-hospital mortality. In the study by Kuramatsu et al.,[5] the prevalence of hyponatremia on admission was 15.60% and in-hospital mortality was doubled in patients who presented with hyponatremia as compared to those who did not (40% vs. 21.1%). In another study by Gray et al.,[17] hyponatremia was associated with longer hospital stay, higher complications, and mortality. Disparity in results could be due to comparatively smaller sample size in our study.

Among the radiological parameters, patients with higher volume of hematoma and midline shift on NCCT head had increased risk for in-hospital mortality. Using ROC curve, cut-off value with optimal sensitivity and specificity for hematoma volume and midline shift were ≥29.5 ml and >5.2 mm, respectively. However, on multivariate logistic regression analysis, neither of the parameters was found to be independent predictor of in-hospital mortality. ICH volume has been so far one of the most consistent outcome predictors. Flemming et al.[2] showed that poor outcome was associated with hemorrhage size of >40 ml and midline shift >6 mm. In the study by Bhatia et al.[6] baseline hematoma volume was an independent predictor of mortality. Wasay et al.[18] also found that mortality was significantly higher (32%) in patients with high volume ICH (>30 ml) as compared to patients with low-volume ICH (6%).

Out of the discharged patients, 80% of the patients had mild disability with mRS of 1–3 and 20% had moderate to severe disability with mRS of 4–5. NIHSS score at the time of hospitalization was found to be the only independent predictor of disability as assessed by mRS score. Our results are not in agreement with the results of two recent studies[6],[13] where majority of (93.3%, 62.9% respectively) discharged patients had higher disability (mRS 4–5). This difference could be due to the difference in clinical severity of the study population at the time of presentation.

One of the major limitations of our study was small sample size as compared to earlier studies. In addition patients were only followed up till their hospital outcome. Furthermore, due to limitation of resources, we did not assess the cause of hyponatremia in the study population.


  Conclusion Top


Our study highlights the facts that SICH is associated with high in-hospital mortality. NIHSS score at the time of hospitalization is an independent predictor of in-hospital mortality as well as degree of disability at discharge. Furthermore, GCS ≤4 and NIHSS >12 at baseline are significant predictors of in-hospital mortality. Hyponatremia is a common occurrence in SICH patients. As hyponatremia is a treatable condition, further studies are required to understand the exact role of hyponatremia on the outcome of SICH patients and whether acute correction of hyponatremia would help in modifying the grave prognosis associated with SICH.

Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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