Treatment of intracerebral haemorrhage

doi:10.1016/S1474-4422(05)70195-2

The Lancet Neurology

Volume 4, Issue 10, October 2005, Pages 662-672

https://doi.org/10.1016/S1474-4422(05)70195-2 Get rights and content

Summary

Apart from management in a specialised stroke or neurological intensive care unit, until very recently no specific therapies improved outcome after intracerebral haemorrhage (ICH). In a recent phase II trial, recombinant activated factor VII (eptacog alfa) reduced haematoma expansion, mortality, and disability when given within 4 h of ICH onset; a phase III trial (the FAST trial) is now in progress. Ventilatory support, blood-pressure reduction, intracranial-pressure monitoring, osmotherapy, fever control, seizure prophylaxis, and nutritional supplementation are the cornerstones of supportive care in intensive care units. Ventricular drainage should be considered in all stuporous or comatose patients with intraventricular haemorrhage and acute hydrocephalus. Given the lack of benefit seen in a the recent STICH trial, emergency surgical evacuation within 72 h of onset should be reserved for patients with large (>3 cm) cerebellar haemorrhages, or those with large lobar haemorrhages, substantial mass effect, and rapidly deteriorating condition.

Introduction

Intracerebral haemorrhage (ICH) is an acute and spontaneous extravasation of blood into the brain parenchyma. ICH accounts for 10–30% of all stroke admissions to hospital, and leads to catastrophic disability, morbidity, and a 6 month mortality of 30–50%.¹ Long-term outcomes are poor; only 20% of patients regain functional independence at 6 months.¹ Although there have been therapeutic advances for aneurysmal subarachnoid haemorrhage and cerebral infarction, treatment for ICH remains limited. Depending on the underlying cause of haemorrhage, ICH is classified as primary or secondary. Primary ICH is when the haemorrhage originates from spontaneous rupture of small arteries or arterioles damaged by chronic hypertension or amyloid angiopathy. Secondary ICH is when haemorrhage results from trauma, rupture of an aneurysm, vascular malformation, coagulopathy, or other causes (panel 1).²

ICH is a common disorder, with an estimated frequency of 37 000–52 000 each year in the USA.3, 4 In a recent population-based study, the overall incidence of ICH was 12–15 cases per 100 000 people per year.⁵ ICH is most common in men, in elderly people, and in Asian and African Americans.¹

ICH results in staggering medical costs because of acute hospital and chronic care expenses and loss of productivity. The cost of ICH is about US$125 000 per patient per year, with an overall cost of $6 billion annually in the USA.4, 6

Section snippets

Risk factors

There are several modifiable risk factors for spontaneous ICH. Hypertension is by far the most important and prevalent risk factor, directly accounting for about 60–70% of cases.7, 8 Chronic hypertension causes degeneration, fragmentation, and fibrinoid necrosis of small penetrating arteries in the brain, which can eventually result in spontaneous rupture.⁹ Some people have discrete arteriolar microaneurysms (Charcot-Bouchard aneurysms) at the site of vessel rupture. These degenerative changes

Clinical manifestations

About half of spontaneous ICH cases originate in the basal ganglia, a third in the cerebral hemispheres, and a sixth in the brainstem or cerebellum. In 40% of cases, ICH is accompanied by intraventricular haemorrhage, which can cause acute hydrocephalus, high intracranial pressure (ICP), and less chance of a good outcome.

Rapid onset of a focal neurological deficit with clinical signs of high ICP—such as an abrupt change in level of consciousness, headache, and vomiting—suggest a diagnosis of

Diagnosis

ICH is confirmed by CT (figure 1). Careful inspection of the pattern and topography of bleeding can sometimes give important clues about a secondary cause of ICH, such as associated subarachnoid blood (suggestive of aneurysm), multiple inferior frontal and temporal haemorrhages (suggestive of trauma), or fluid-fluid levels within the haematoma (indicative of coagulopathy; figure 2). The volume of the haemorrhage can be rapidly estimated at the bedside from the CT with the ABC/2 method, which

Pathophysiology

Understanding of the pathophysiology of ICH has changed a lot in recent years. What was thought to be a simple and rapid bleeding event is now understood to be a dynamic and complex process that involves several distinct phases. The two most important new concepts are that many haemorrhages continue to grow and expand over several hours after onset of symptoms—a process known as early haematoma growth—and that most of the brain injury and swelling that happens in the days after ICH is the

Prognosis

Mortality after ICH approaches 50% at 1 year.48, 49 Half of all deaths happen in the first 2 days after symptom onset;⁵⁰ whereas most deaths that take place after the first month are the result of secondary medical complications. Independent predictors for 30 day and 1 year mortality include large ICH volume, coma, older age, intraventricular haemorrhage, and infratentorial location.48, 49, 50 A useful clinical grading scale (the ICH score) that incorporates these five elements allows rapid

Airway

Rapid neurological decline and depressed consciousness lead to loss of normal reflexes that maintain an open airway, which mandates immediate endotracheal intubation and mechanical ventilation.⁵⁵ Failure to recognise imminent airway loss can result in aspiration, hypoxaemia, or hypercapnia, which in turn can lead to cerebral vasodilatation and high ICP. For rapid sequence intubation, many practitioners prefer sedatives (such as propofol and etomidate) and non-depolarising neuromuscular

Positioning of patients

To minimise ICP and reduce the risk of ventilator-associated pneumonia in mechanically ventilated patients, the head should be elevated 30 degrees.

Fluids

Isotonic fluids such as 0·9% saline (about 1 mL/kg/h) should be given as the standard intravenous replacement fluid for patients with ICH. Free-water given in the form of 0·45% saline or 5% dextrose in water can exacerbate cerebral oedema and increase ICP because it flows down its osmotic gradient into injured brain tissue.79, 80 Solutions containing

Surgical management

The STICH trial, a landmark trial of 1033 ICH patients, showed that emergent surgical haematoma evacuation within 72 h of onset does not improve outcome in comparison to a policy of initial medical management.¹⁰⁴ These results are consistent with those of a meta-analysis of all prior trials of surgical intervention for supratentorial ICH, which showed no benefits.¹⁰⁵ Although the STICH trial has rightfully dampened the enthusiasm of neurosurgeons for surgery, it must be remembered that the

Future directions

For decades, the prevailing attitude toward the treatment of ICH has been one of therapeutic nihilism. There is a need for more evidence to place aggressive intensive-care-unit treatment for ICH on firmer scientific footing. The results of the phase II trial of rFVIIa for ICH are encouraging; an effective emergency treatment for ICH may soon be available. If this is the case, future efforts could be directed at testing the efficacy of combining very early surgery with acute haemostatic therapy,

Search strategy and selection criteria

References for this review were identified by searches of Ovid, MEDLINE, and PubMed from 1966 until April 2005 for the term “intracerebral hemorrhage”. Articles were also identified through searches of the authors' own files, and from reference lists of articles identified in the literature search. Only papers published in English were reviewed.

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Cited by (271)

A Cost Utility Analysis of Minimally Invasive Surgery with Thrombolysis Compared to Standard Medical Treatment in Spontaneous Intracerebral Haemorrhagic Stroke
2021, Journal of Stroke and Cerebrovascular Diseases
Standard medical management of spontaneous intracerebral haemorrhage (ICH) and surgical hematoma evacuation starkly differ, and whilst landmark randomised control trials report no clinical benefit of early surgical evacuation compared with medical treatment in supratentorial ICH, minimally invasive surgery (MIS) with thrombolysis has been neglected within these studies. However, recent technological advancements in MIS have renewed interest in the surgical treatment of ICH. Several economic evaluations have focused on the benefits of MIS in ischaemic stroke management, but no economic evaluations have yet been performed comparing MIS to standard medical treatment for ICH.
All costs were sourced from the UK in GBP. Where possible, the 2019/2020 NHS reference costs were used. The MISTIE III study was used to analyse the outcomes of patients undergoing either MIS or standard medical treatment in this economic evaluation.
The incremental cost-effectiveness ratio (ICER) for MIS was £485,240.26 for every quality-adjusted life year (QALY) gained. Although MIS resulted in a higher QALY compared to medical treatment, the gain was insignificant at 0.011 QALY. Four sensitivity analyses based on combinations of alternative EQ-5D values and categorisation of MIS outcomes, alongside alterations to the cost of significant adverse events, were performed to check the robustness of the ICER calculation. The most realistic sensitivity analysis showed a potential increase in cost effectiveness when clot size is reduced to <15ml, with the ICER falling to £74,335.57.
From the perspective of the NHS, MIS with thrombolysis is not cost-effective compared to optimal medical treatment. ICER shows that intention-to-treat MIS would require a cost of £485,240.26 to gain one extra QALY, which is significantly above the NHS threshold of £30,000. Further UK studies with ICH survivor utilities, more replicable surgical technique, and the reporting of clot size reduction are indicated as the present sensitivity analysis suggests that MIS is promising. Greater detail about outcomes and complications would ensure improved cost-benefit analyses and support valid and efficient allocation of resources by the NHS.
Decompressive Craniectomy for Infarction and Intracranial Hemorrhages
2021, Stroke: Pathophysiology, Diagnosis, and Management
Patients with subtotal or complete infarction of the middle cerebral artery (MCA) territory are at high risk for space-occupying edema formation and increased intracranial pressure (ICP). The diagnosis of malignant MCA infarction is based on clinical and radiologic criteria. Patients who present with a severe hemispheric syndrome, deterioration of consciousness with reduced ventilator drive, and definite infarction on neuroimaging of at least two-thirds of the MCA territory including the basal ganglia are at high risk for malignant brain edema. Medical therapies have not been proven effective in clinical trials, but they may be considered in addition to decompressive hemicraniectomy for patients who deteriorate due to increased ICP. Decompressive hemicraniectomy for malignant MCA infarction increases the odds of survival, but is associated with increased rates of severe disability, especially in patients older than 60 years. Therefore, the decision toward surgery should be taken on an individual basis after advising patients and families about potential outcome states. In large space-occupying cerebellar infarction with clinical deterioration, ventriculostomy (extraventricular drainage [EVD]) should be considered if hydrocephalus is present. Otherwise, suboccipital decompressive craniectomy (SDC) with or without strokectomy can be considered, depending on the specific features of the individual patient. In cerebellar hemorrhage, surgical hematoma evacuation and/or EVD placement are frequently performed in patients with large (>3 cm) hematoma, basal cistern, and brainstem compression, and clinical deterioration due to hydrocephalus. Decompressive craniectomy is not the treatment of first choice for spontaneous cerebral hemorrhage or subarachnoid hemorrhage. It may, however, be considered for the treatment of refractory increased ICP in these disorders.
Specificities of acute phase stroke management in the elderly
2020, Revue Neurologique
Health professionals are currently facing the challenge of managing an increasing number of old patients presenting with acute stroke, due to rapid aging of the population. Compared to their younger counterparts, elderly patients differ in many ways in the setting of acute stroke. Apart from a striking high stroke incidence, which increases exponentially as age increases, cardioembolism also becomes, as patients age, the main cause of ischemic stroke. Delirium, which can challenge the diagnosis, is frequent at the acute phase of stroke, and may be related to an underlying dementia, which is almost exclusively observed in the elderly during stroke. At all levels, management of elderly stroke patients is suboptimal, especially when they are cognitively impaired, with insufficiencies including admission to stroke units, applying standards of care and investigation, reperfusion therapy for ischemic stroke, and finally transfer to rehabilitation centers. A paradigm shift must take place to limit age-related discrimination for acute-phase management of stroke.
Hypothermia and temperature modulation for intracerebral hemorrhage (ICH): pathophysiology and translational applications
2024, Frontiers in Neuroscience
Laser navigation combined with XperCT technology–assisted puncture of basal ganglia intracerebral hemorrhage
2023, Neurosurgical Review
Assessment of the Extent of Intracerebral Hemorrhage Using 3D Modeling Technology
2023, Healthcare (Switzerland)

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ReviewTreatment of intracerebral haemorrhage

Summary

Introduction

Section snippets

Risk factors

Clinical manifestations

Diagnosis

Pathophysiology

Prognosis

Airway

Positioning of patients

Fluids

Surgical management

Future directions

Search strategy and selection criteria

Neurol Clin

Neurosurg Clin N Am

Am J Med

Mayo Clin Proc

Chest

Epidemiology of intracerebral hemorrhage

Spontaneous intracerebral hemorrhage

N Engl J Med

Guidelines for the management of spontaneous intracerebral hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association

Stroke

Lifetime cost of stroke in the United States

Stroke

Inpatient costs of specific cerebrovascular events at five academic medical centers

Neurology

Hypertension as a risk factor for spontaneous intracerebral hemorrhage

Stroke

Three important subgroups of hypertensive persons at greater risk of intracerebral hemorrhage

Hypertension

Pathological observations in hypertensive intracerebral hemorrhage

J Neuropathol Exp Neurol

Blood pressure control and recurrence of hypertensive brain hemorrhage

Stroke

Five-year findings of the hypertension detection and follow-up program III: reduction in stroke incidence

JAMA

The decreasing incidence of primary intracerebral hemorrhage: a population study

Ann Neurol

Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage

Stroke

Heavy drinking, but not moderate or intermediate drinking, increases the risk of intracerebral hemorrhage

Epidemiology

Low cholesterol as a risk factor for primary intracerebral hemorrhage: a case-control study

Neuroepidemiology

Nonaspirin nonsteroidal anti-inflammatory drugs and risk of hospitalization for intracerebral hemorrhage: a population-based case-control study

Stroke

Use of aspirin, epistaxis, and untreated hypertension as risk factors for primary intracerebral hemorrhage in middle-aged and elderly people

Stroke

The Harvard Cooperative Stroke Registry: a prospective registry

Neurology

The ABCs of measuring intracerebral hemorrhage volumes

Stroke

Three-dimensional computerized tomography angiography in patients with hyperacute intracerebral hemorrhage

J Neurosurg

Extravasation of radiographic contrast is an independent predictor of death in primary intracerebral hemorrhage

Stroke

Comparison of MRI and CT for detection of acute intracerebral hemorrhage

JAMA

Spontaneous intracranial hemorrhage: which patients need diagnostic cerebral angiography? A prospective study of 206 cases and review of the literature

Stroke

The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow-up assessment

J Neurosurg

Relative edema volume is a predictor of outcome in patients with hyperacute spontaneous intracerebral hemorrhage

Stroke

Early hemorrhage growth in patients with intracerebral hemorrhage

Stroke

Ultra-early hemostatic therapy for intracerebral hemorrhage

Stroke

Perilesional blood flow and edema formation in acute intracerebral hemorrhage: a SPECT study

Stroke

Neurologic deterioration in noncomatose patients with supratentorial intracerebral hemorrhage

Neurology

Progression of mass effect after intracerebral hemorrhage

Stroke

Dynamic single-section CT demonstrates reduced cerebral blood flow in acute intracerebral hemorrhage

Cerebrovasc Dis

Reversible ischemia around intracerebral hemorrhage: a single-photon emission computerized tomography study

Review
Treatment of intracerebral haemorrhage