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Research article | DOI: https://doi.org/10.31579/2642-973X/043
1 Department of Neurology, Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia.
2 Department of Neurology, Siloam Hospital Lippo Village, Tangerang, Indonesia.
*Corresponding Author: Yusak Mangara Tua Siahaan
Citation: Yusak Mangara Tua Siahaan, Retno Jayantri Ketaren, Jacqueline Tasha Margono, Winona Jennifer. (2020). Effect of Hypoxia on Severity Outcome of Early Onset Acute Ischemic Stroke: A Correlative Study and Review. J. Brain and Neurological Disorders. 5(5): DOI:10.31579/2642-973X/043
Copyright: 2022 Yusak Mangara Tua Siahaan. This is an open-access article distributed under the terms of The Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 27 October 2022 | Accepted: 01 November 2022 | Published: 08 November 2022
Keywords: acute ischemic stroke; hypoxia; prognostic factor; nihss score
Background And Objective
Stroke is the leading cause of long-term disability. One of the factors that play a role in exacerbating stroke is hypoxia. Hypoxia in the early onset of acute stroke can cause significant side effects in ischemic brain areas and may cause different neurological consequences depending on multiple factors. We hypothesized that the oxygen saturation level in the early days of acute onset would correlate with the outcome of patients with acute ischemic stroke. This study investigated the association between oxygen saturation in early onset acute ischemic stroke and the National Institutes of Health Stroke Scale (NIHSS) score.
Materials and methods
We conducted a cross-sectional study at Siloam Hospital, Lippo Village, between January and April 2021. Research data were collected from the medical records of patients with the first onset of acute ischemic stroke who met the inclusion and exclusion criteria. Data were processed using a chi-square test with IBM SPSS 26.0.
Results
95 Subjects (mean age 59.20 ± 1.254) were collected. The study showed significant association between hypoxia and higher NIHSS scores (p = 0.001, odds ratio [OR] = 0.099, confidence interval [CI] 95% = 0.021–0.461).
Heart diseases such as congenital heart disease, coronary heart disease, and heart failure showed a significant association with higher NIHSS scores and lowered oxygen saturation levels (p = 0.023, OR (95%CI) 0.265 (0.080–0.880).
Conclusion
Our study indicates that a lower oxygen saturation level at early onset correlates with a higher NIHSS score and is associated with a poor prognosis. Oxygen supplementation in patients with ischemic stroke is crucial for better outcomes
Stroke is the second leading cause of death worldwide, with a mortality rate of 5.5 million deaths per year. [1,2] The mortality rate is worse in developing countries, where the management of stroke is not well established. Interrupted blood flow can lead to a lack of oxygenation of the brain cells, causing apoptosis and necrosis of the brain, which manifests as neurological deficits [3–5]. In addition, stroke causes a high disability rate in surviving patients, creating not only short-but also long-term permanent problems. Thus, acute management of stroke is pivotal[1,2]
These neurological deficits vary in symptoms and severity depending on the location and extent of the lesion in the brain [3]
Many scales are currently used to assess the progression of stroke, including the National Institutes of Health Stroke Scale (NIHSS) [6]
The severity of stroke is highly dependent on establishing the correct diagnosis and treatment, especially regarding the onset of events, arrival at the hospital, and other predisposing factors that occur at the time of stroke. One of the important factors that play a role in exacerbating stroke is hypoxia [7].
Hypoxia is commonly found in stroke patients in the early days of hospitalization and is associated with higher mortality and morbidity rates. However, hypoxic conditions are often underdiagnosed and untreated, which may be attributed to conditions complicated by stroke, such as aspiration and respiratory dysfunction. Hypoxia that occurs in the first few hours can cause significant side effects in ischemic brain areas and, if left untreated, may cause different neurological consequences depending on multiple factors such as onset, the severity of hypoxia, and level of tissue perfusion [7,8]
The American Heart Association/American Stroke Association guidelines recommend administering oxygen supplementation to maintain oxygen saturation > 94% in stroke patients [9]
Comprehensive management of stroke is essential for better patient outcomes. Therefore, the present study was conducted based on the hypothesis that the oxygen saturation level at acute onset would correlate with the outcome of patients with acute ischemic stroke.
We conducted a single-center cross-sectional study at Siloam Hospital, Lippo Village, between January and April 2021. Research data were collected from the medical records of patients treated in the stroke unit with the first onset of acute ischemic stroke. Data were collected using consecutive sampling, and the patients with their first acute ischemic stroke with an onset of < 48>
Oxygen saturation was measured by pulse oximetry for 2 min, and the NIHSS score was obtained at admission. Neurologists confirmed the diagnosis of ischemic stroke based on the physical and neurological examination in combination with the results of computerized tomography (CT) [9]
Other patient information, such as a history of hypertension, diabetes mellitus (DM), heart disease, dyslipidemia, and smoking, was also collected for demographic data. Results with a p-value < 0>
Data were processed using IBM SPSS 26.0 (Statistical Package for the Social Sciences, IBM Corp., Armonk, NY, USA) and analyzed using the chi-square statistical test method and Logistic Regression model The Pelita Harapan University Ethics Committee approved our study (ethical review number 041/K-LKJ/ETIK/I/2021).
Table 1: Baseline Characteristics of the patients
Ninety-five subjects were included in this study, with male predominance (61%). Most patients were between 51 and 60 years old (34.2%, n: 25). The mean age was 59.20 ± 1.254 years. The data distribution showed 81.05% of subjects with normal saturation levels (95%–100%) and 18.94% with hypoxia (< 95>
The study showed significant correlation between hypoxia and higher NIHSS scores (p = 0.001, odds ratio [OR] = 0.099, confidence interval [CI] 95% = 0.021–0.461).
Risk factors such as sex, hypertension, diabetes mellitus, dyslipidemia, and smoking habits were not significantly correlated with higher NIHSS scores. However, heart diseases such as congenital heart disease, coronary heart disease, and heart failure significantly correlate with higher NIHSS scores and lowered oxygen saturation levels (p = 0.023, OR 0.265, 95% CI = 0.080–0.880).
Multivariate logistic regression data showed that, among other independent variables, only heart disease and oxygen saturation levels influenced the NIHSS score (p = 0.043, p = 0.003, respectively).
A negative Pearson correlation test indicated that this study's lower oxygen saturation level correlated with a higher NIHSS score and vice versa (p = -0.318).
Table 2. Chi- Square Univariate data
Table 3. Multivariate Data Logistic Regression
Oxygen saturation (SpO2) measurement using pulse oximetry is one of the blood oxygen level measurement methods that is widely available and cost-effective7. This method has been proven reliable in assessing oxygen saturation, especially > 90%. Hypoxia is a condition where the oxygen saturation is < 95> 90%. The present study showed that 18.94% of subjects had low oxygen saturation < 95>
Another study reported that the oxygen extraction fraction (OEF) increases during acute stroke. OEF, defined as the ratio of blood oxygen tissue from the blood flow, acts as one of the two compensatory mechanisms when cerebral perfusion pressure (CPP) falls, highlighting the importance of adequate oxygen delivery in stroke[11].
Hypoxia during the first few days after a stroke may adversely affect cells in the ischemic penumbra, worsening neurological deficits and clinical outcomes.
The condition of neurological deficits can be assessed using the NIHSS score. The current study presented 62.1% of subjects with a moderate to severe NIHSS score (NIHSS ≥ 5) and showed significant correlation with oxygen saturation < 95 p =0.001), xss=removed xss=removed>
One of the most important findings of this study is the negative Pearson correlation test, which indicates that a lower oxygen saturation level correlates with a higher NIHSS score and vice versa (p = -0.318). This result showed that even a slight decrease in the normal oxygen saturation range (95%–99%) would also give rise to higher NIHSS scores. These findings indicate that a disproportion in cerebral tissue supply and oxygen
demand promotes a sequence of biochemical and molecular events that lead to neuronal cell death.
Oxygen is essential for the survival of aerobic organisms and is crucial for the survival of the penumbra during ischemic stroke. Therefore, oxygen saturation is essential to maintaining the penumbra 12]. Severe and prolonged reductions in cerebral blood flow following low oxygen saturation levels lead to more deprivations in oxygen and glucose delivery, leading to the build-up of potentially toxic substances.
The pathophysiology of ischemic stroke at the cellular level is composed of numerous processes, including increased intracellular calcium levels, excitotoxicity, free radical-mediated toxicity, cytokine-mediated toxicity, activation of glial cells, and infiltration of leukocytes, which can later lead to ischemic necrosis. Cerebral ischemia results in a dramatic reduction in blood flow and subsequent necrotic cell death [15]. These hemodynamic changes can reduce ATP, causing metabolic stress, energy failure, ionic perturbations, and ischemic injury. This incidence is highly threatening for neurons, as the brain is vulnerable to oxidative stress due to its high rate of oxidative metabolic activity [14,16].
Oxidative stress may lead to calcium accumulation, mitochondrial dysfunction, and production of reactive oxygen radicals, which are essential cell death mechanisms following ischemic insults [15,16]
To summarize, hypoxia at the early onset can lead to significant side effects in ischemic brain areas, which are associated with poor prognosis, higher NIHSS score, and higher mortality rate [6,9.17,18].
Further, our study found that heart diseases such as congenital heart disease, coronary heart disease, and heart failure showed a significant correlation with higher NIHSS scores and lowered oxygen saturation levels. Moreover, multivariate logistic regression data showed that, among other independent variables, only heart disease and oxygen saturation levels influenced the NIHSS score. The results of this study indicate that cardiovascular disease can induce hypoxia during the early onset of acute stroke and lead to the worsening of the stroke condition. This is because the heart is a circulatory system that distributes blood flow to each tissue and transports oxygen and nutrients. Disturbance in the circulatory system would decrease oxygen delivery, leading to tissue hypoxia, which occurs in several cardiovascular disorders, including atherosclerosis, pulmonary arterial hypertension, and heart failure. This would also explain how cardiovascular disease worsens the prognosis of patients with stroke [19,20].
The accuracy of the criteria for early stroke onset needs to be emphasized so that each sample has the same range of onset
Our study indicates that a lower oxygen saturation level at early onset correlates with a higher NIHSS score and is thus associated with a poor prognosis. Oxygen supplementation is crucial for better outcomes in patients with ischemic stroke.
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