Medicosnext
Abstract
Spontaneous intracerebral hemorrhage is the most devastating and debilitating type of stroke. It is defined as bleeding in the brain parenchyma in the absence of trauma. It is the main reason for death and disability in Australia. ICH accounts for 10-20% of all stroke types and has poor forecast compared to ischemia. Various risk factors associated with ICH have been identified. Despite its tremendous effect on health, there is no proven treatment to improve outcome. The available medical and surgical management remains controversial, and treatment consists more of conservative and supportive management.
Introduction
Spontaneous intracerebral hemorrhage (ICH) is a classification of stroke that is characterized as non-traumatic bleeding into the brain parenchyma, which can spread into the ventricles and the subarachnoid space [1,2,3]. The principal source of demise and disability in Australia is stroke [4]. Stroke is also the second fundamental reason of death and fourth main cause of longstanding disability globally [5]. Intracerebral hemorrhage is a substantial cause of mortality and morbidity, accounting for 10-20% of all strokes, despite significant medical advancement. It is not only associated with poor prognosis, but also has the highest mortality rate of all stroke subtypes [6]. The World Health Organization stated in 2004 that around 5.71 million people died from stroke, and estimated that the number will rise up to 7.8 million by 2030 [7,8].
Intracerebral hemorrhage is a medical emergency. Speedy diagnosis and effective management is crucial. The need for aggressive early management is pivotal, because ICH carries the risk of initial neurological worsening, and is linked with extreme rate of significant enduring outcomes. Following the first year, more than 75% of all ICH patients are severely incapacitated or deceased. This clearly makes ICH a major health burden that needs more effective ways of treatment and management [9].
Spontaneous intracerebral hemorrhage is categorized as either primary or secondary. Primary intracerebral hemorrhage develops in the absence of any fundamental vascular malformation and coagulopathy. It is classified by its location, and is more common than secondary intracerebral hemorrhage. More than 80% of primary ICH is the result of hypertensive arteriosclerosis and cerebral amyloid angiopathy [10,11,12]. Likewise, secondary ICH is related with congenital and developed conditions, such as intracranial tumor, vascular malformation, coagulopathy, and hemorrhagic transformation of an ischemic stroke, drug use, cerebral venous thrombosis, and cerebral vasculitis [10,11,12,13].
Intracerebral hemorrhage not only lags behind ischemic event in incidence, but also lags far behind in the treatment option.The management still remains controversial, and case fatalities post ICH has not changed over the past two decades [14]. Treatment mainly remains supportive, as there are no approved therapies that improve outcomes, making ICH a huge burden to the healthcare system [9,15].The aim of this literature review is to identify and shed light on all the available resource and studies on intracerebral hemorrhage and its management.
Methods
An electronic search was performed using Ebscohost, Proquest, CINHAL, and PubMed databases. The search was also extended to National Stroke Foundation, American Heart Association, and Journal of Neurological Disorder and Stroke, using the search terms cerebrovascular accident, stroke, intracerebral hemorrhage, spontaneous bleed, types of stroke, management of spontaneous bleed, and clinical trials on ICH and available management. The search was restricted to obtain recent and relevant articles. It was limited to full text journal articles and peer-reviewed articles in the English language. Numerous works from previous times were also encompassed due to their abundant support in the chosen area. To pursue further appropriate sources, the identified literature reference lists were also evaluated. Even though there are limited studies and clinical trials that show effective intracerebral hemorrhage management, there was overwhelming literature available on the database and internet on intracerebral hemorrhage and management. The selection of literature was based on randomized control trials, observational studies, clinical trials, meta-analysis, and Cochrane systemic review. The literature was limited to nature of stroke; ischemic stroke was not included in this review.
Risk Factors
The case fatality rate varies from 35% at day 7 to 59% at one year [3]. Patients are left behind with severe debility, with less than 40% of patients recovering with full functional independence [3]. With better control of risk factors, the epidemiology of ICH may change in the upcoming days.
Race: Non-traumatic ICH is more common in the Asian population; it is also twice as common in black population compared to whites [16].
Age: A meta-analysis published in 2003 reported substantial connection between age and increased risk of an ICH [16]. The principal risk factor in elderly population is cerebral amyloid angiopathy [17].
Sex: Men above 55 years have higher occurrence of spontaneous ICH than women [16,17].
Hypertension: The utmost critical modifiable risk factor is chronic arterial hypertension [3, 16]. 50-70% of people who develop ICH have chronic hypertension [3]. It particularly increases risk in the older population [16]. It also doubles the risk in patients younger than 55 years old, especially those who have ceased taking antihypertensive [17].
Cholesterol: Various cohort studies, cardiac trials, and studies like “Stroke prevention by aggressive reduction in cholesterol levels” (SPARCL) have shown association of low cholesterol level with ICH; however, this still remains controversial, as this is linked with cholesterol-lowering agent post ischemic stroke. This requires more intensive study and trials [16,17].
Alcohol: Moderate to heavy and chronic alcohol abuse has a connection with ICH [16,17]. Alcohol intake may affect coagulation, enhance vascular fragility, and platelet function [17].
Smoking: Smoking’s association with ICH is controversial [16,17]. However, smokers with hypertension have increased risk [17].
Ethnicity, psychosocial, and socioeconomic dynamics also play important roles in the frequency of cerebral hemorrhage, with ICH being twice as common in developing and third world countries compared to developed countries [3]. Lack of education and awareness of primary healthcare system is the key to higher incidence [16].
These dominant factors may provoke secondary vascular changes, like arterial aneurysms and small vessel disease, which may ultimately result in intracerebral hemorrhage [14].
Oral Anticoagulation
The use of oral anticoagulation (OAC) has increased in the last decade for the prevention and management of deep venous thrombosis, valvular dysfunction, and ischemic stroke related to atrial fibrillation (AF) [17,18]. It escalates the risk of ICH by 5 to 10 times in overall population, and around 15% of events is associated with its use [17]. With the increase in aging population, a high occurrence of AF is anticipated, with the number of patients on lifelong oral anticoagulation expected to rise [18,19]. The new direct oral anticoagulants (DOAs) have considerably lower rates of ICH, as compared to vitamin K antagonist, such as warfarin [18]. However, there are no reversing agents for newer DOAs. Warfarin can be reversed with vitamin K agonist agents [17,18,19,20]. In the setting of OAC-related ICH, the prime aim is to withhold the drug and reverse the medication’s effects by administration of counter agent when accessible, and monitor the reversal efficiency with laboratory findings. OAC-related ICH is associated with larger hematoma size and higher mortality rates [3]. It is important that care providers recognize their use in the initial evaluation, so that the treatment strategy is appropriate [20].
The prime cause of spontaneous intracerebral hemorrhage appears to be the pathophysiological modification in the blood vessel wall, resulting in breakup of the small arteries and arterioles [16]. Not a single individual treatment for ICH has revealed advantage in randomized control trial [9]. Original hematoma capacity and expansion remains the biggest factor in death and functional outcome [9]. The treatment and management of ICH predominantly remains conservative. Numerous issues regarding managementof ICH remains unanswered. Recent studies and clinical trials have improved our perception of ICH management as blood pressure control, hemostatic therapy, and hematoma evacuation [3].
Medical Management
Blood pressure management
The main risk factor for the progress of spontaneous ICH is chronic hypertension [3]. Patients presenting with ICH often have very elevated blood pressure [13]. Raised blood pressure is linked with hematoma enlargement, neurological deterioration, and poor consequence [13]. In the earlier days, aggressive lowering of blood pressure was contraindicated, however, recent studies like Phase 3, INTERACt-2, ATACH-2 have shown that aggressively lowering blood pressure improves functional outcome [3,13]. Initial treatment should begin with intravenous antihypertensive followed by oral antihypertensive, which should be added to the regime to maximize the benefit.
Hemostatic agents
There are very limited literature and clinical trials showing the benefit of pharmacological agents like anti-fibrinolytic agents to limit the hematoma volume [21]. Volume of ICH influences outcome, and about a third of acute ICH increases within 24 hours of onset. Early treatment with haemostatic agent may improve result by preventing hematoma volume and reducing further expansion [14]. Single-blinded randomized control trial on anti-fibrinolytic agents like tranexamic acid showed that it is very useful in stabilizing hematoma if the blood pressure is well controlled [22].
Surgical Management
Surgical management option also remains questionable. The rationale for surgical evacuation of hematoma circles around the ideas of avoiding brain herniation, reducing intracranial pressure, and decreasing the pathophysiological effect of hematoma on the adjacent tissues [20]. Randomized control trials of computer tomography scan confirming supratentorial hemorrhage exhibited that surgery reduced the likelihood of being dead or dependent compared to medical management alone [23]. The only available clinical trial in this setting is the STICH trials 1and 2, which emphasized evacuating hematoma via craniotomies. This study did not show any difference in the ICH management with medical treatment in conjunction with surgical management [24]. However, STICH 1 showed improvement with surgery in ICH with presence of intraventricular hemorrhage andhydrocephalus, which are the factors for poor outcome [25]. Stereotactic-guided evacuation of hematoma is better option, compared to open craniotomy [26,27].
Additional Management
As there are only limited primary treatment options for spontaneous intracerebral hemorrhage, these too remain uncertain at some point, so secondary management options are implied in ICH management.
Glucose management
Elevated blood glucose is linked with enlarged consequences of morbidity and mortality and poor outcomes in patients with ICH, irrelevant of presence of diabetes mellitus. Strict blood glucose monitoring and control is interrelated with decrease in intracranial pressure and seizure activities [17]. The acute toxicity of hyperglycemia has much worse side effect in critically ill patients [17]. Hypoglycemia should be avoided, as well [20].
Temperature management
Pyrexia is common after ICH, particularly with intraventricular hemorrhages. It can also be related to hematoma growth, and should be treated aggressively [17,20]. High fevers are associated with poor outcomes. Elevated brain temperature is correlated with cerebral edema and raised intracranial pressure [17].
Seizure management
Patients with ICH have a higher risk of mounting seizures than ischemic stroke [16]. The incidence of seizure activity is 16% high post ICH [20]. This can be related to worsening neurological condition and midline shift [16]. The American Heart Association guidelines suggest the use of anticonvulsant therapy for the prevention of seizure activities for up to one month, and should be slowly weaned off when there are no signs of seizure activities [14,16].
Deep vein thrombosis (DVT) prophylaxis
Clients with ICH have higher incidence of DVT and pulmonary embolism (PE). Patients with ICH are described to have up to four folds greater risk of having DVT than ischemic stroke [3]. This complication can be lethal because of limb paresis and prolonged bed rest and immobilization [17]. The CLOT trials (1,2, and 3) show the benefit of pneumatic calf compressor in reducing the prevalence of DVT [20]
Dysphagia/nutrition
Dysphagia is common after stroke. It is connected with increased risk of pneumonia [3]. Nutrition should be started within 48 hours of onset of bleed to reduced malnutrition and refeeding syndrome [17].
Discussion
Annually, more than one million people are affected by intracerebral hemorrhage [13]. It is the most debilitating type of stroke. However, there is clearly no proven effective treatment available for this fatal disease, leaving a huge burden on the healthcare system, patients, families, and caregivers [9]. The lack of consensus for the treatment of ICH has led to great disparity in medical and surgical management [27]. As mentioned above, the primary management is blood pressure control, surgical evacuation, and hemostatic agent use. This discussion focuses on the obvious literature gaps and shortcomings in the primary management guide for ICH.
From clinical experience, blood pressure management is the only practical management therapy practiced in hospitals; however, aggressive blood pressure lowering strategies remain debatable [28]. The two big trials—INTERACT 2 and ATACH 2—looked into the benefits of aggressively lowering blood pressure in spontaneous intracerebral hemorrhage groups [28]. INTERACT 2 randomized 2,839 ICH patients with target systolic blood pressure (SBP) less than 140 and less than 180 within six hours of onset of symptom. The death and disability ratio was 52% and 55.3%, respectively [28]. There was no difference in both target SBPs.
Likewise, ATACH 2 randomized 1,000 ICH patients with 4.5 hours of symptom onset and divided the group into aggressive and conservative SBP strategies [28]. The research investigators concluded that outcomes had no significant benefit with assertive lowering of blood pressure, as the result displayed 38.7% (aggressive treatment) and 37.7% (conservative treatment)[28]. Aggressive blood pressure reduction after ICH may be inclined to reduce cerebral perfusion pressure, leading to ischemia accompanied by increased intracranial pressure, resulting in further neurological damage [17].
Currently, there is no Food and Drug Administration (FDA) approved pharmacological agent for the treatment of ICH [29]. The Cochrane review of hemostatic drug post-publication of phase III randomized control trial rFVIIa showed no evidence of reduced death and dependency due to the use of hemostatic drug in ICH patients [21]. Hemostatic agents were associated with heart attack and DVT [14]. This available option is also surrounded with arguments and is not common line of treatment in hospital from clinical experience.
Now, this leaves us with surgical management, which is full of debate, as well. It has not been proven to be favorable in randomized control trials. The biggest trial, STICH, also failed to show the benefit, leaving no hope in the treatment option [9]. Surgical intervention is also based on the area and size of the hematoma [13].
There is various published data on the management on ICH, however, none of these data sheds light in the progress and ways to tackle this deadly incidence.
Conclusion
Intracerebral hemorrhage is a medical emergency with highest risk of morbidity and mortality. Early effective treatment can reduce the morbidity and mortality and reduce long-term disability. The crucial management includes blood pressure management, identifying anticoagulation related hemorrhage and reversing if applicable, and consideration of surgical management and hemostatic agent use. Ongoing vigorous research is needed for prevention and effective treatment to decrease the disease burden and improve outcome.
