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The management of spontaneous primary intracerebral haemorrhage
NEUROINTENSIVE CARE
The management of spontaneous primary intracerebral haemorrhage
Learning objectives After reading this article, you should be able to: C describe the initial assessment and management of acute intracerebral haemorrhage C identify the causes of Intracerebral haemorrhage C identify the prognostic factors in intracerebral haemorrhage
Christopher J Taylor
Abstract
Causes and risk factors
Intracerebral haemorrhage (ICH) accounts for around 10e20% of all strokes and results from a variety of disorders. ICH is more likely to result in death or major disability than ischaemic stroke or subarachnoid haemorrhage. Rapid imaging allows early diagnosis and characterization of the localization and severity of the haemorrhage. Patients with significant acute ICH should be managed in a critical care unit. Treatment entails general supportive care, control of blood pressure and intracranial pressure, prevention of haematoma expansion and, where indicated, neurosurgical intervention. In those patients whose bleed extends into the ventricular system or who have infratentorial bleeds are at increased risk of associated hydrocephalus, rapidly increasing intracranial pressure requiring urgent CSF drainage. The 30-day mortality from intracerebral haemorrhage ranges from 35 e52%. Among survivors, the prognosis for functional recovery depends upon the location of haemorrhage, size of the haematoma, level of consciousness, the patient’s age, and overall medical condition.
Primary ICH is strongly associated with a number of risk factors or structural abnormalities, which include: hypertension e present in 40e60% of patients cerebral amyloid angiopathy (CAA). medication: anticoagulants coagulopathies smoking sporadic cerebral amyloid angiopathy drugs of abuse (alcohol but, particularly, cocaine and amphetamine) vasculitis diabetes mellitus. Hypertension is the single most important risk factor for primary ICH. Multiple meta-analyses have suggested hypertension >160/90 increases the risk of intracerebral haemorrhage by more than nine times. After hypertension, the second most important risk factor is thought to be due to cerebral amyloid angiopathy: the accumulation of beta amyloid within the media and adventitia of cerebral blood vessels disrupting their structure increasing the chance of blood leakage and rupture. Medication in the form of anticoagulants (e.g. warfarin), antiplatelets drugs (e.g. aspirin and clopidogrel) and newer agents (e.g. factor 10 inhibitors such as rivaroxaban) all increase the risk of ICH; however, the benefits of these drugs far outweigh the risks associated with their use.
Keywords Intracerebral haemorrhage; intracranial haemorrhage Royal College of Anaesthetists CPD Matrix: 2F01
Intracranial haemorrhage Intracranial haemorrhage may be intracerebral, subarachnoid, subdural or extradural. Approximately 10e20% of stroke is caused by intracerebral haemorrhage (ICH) and is the second most common form of stroke after ischaemic stroke with an annual incidence of 20e25/100,000 of the UK population. The incidence increases significantly after the age of 55 years and doubles with each decade to the age of 80.1,2 Intracerebral haemorrhage can occur as a complication of a pre-existing brain lesion, such as a tumour, recent infarct or vascular malformation and is referred to as secondary intracerebral haemorrhage. This article will only focus on ‘primary’ spontaneous intracerebral haemorrhage, that is, Intracerebral haemorrhage or bleeding into the brain parenchyma in the absence of a clear underlying lesion. The article will review the potential causes, risk factors, presentation, investigations, management and prognosis of this important condition.
Clinical presentation and syndromes of intracranial haemorrhage Primary ICH occurs following the rupture of a blood vessel within the brain parenchyma with the sudden development of haematoma of variable size that slowly enlarges over hours or days, especially in patients on anticoagulants, leading to progressive focal neurological deficit and deterioration in conscious level secondary to mass effect. Headache, vomiting and a decreased level of consciousness develop if the haematoma becomes sufficiently large. Seizures in the first days after ICH occur in <30%; the development of stupor or coma is an ominous sign. Neurological signs vary depending upon the location of the haemorrhage. Deep haemorrhage especially into the putamen is especially associated with hypertension and occurs in approximately 35%, subcortex in 30% and, less commonly, into the cerebellum, thalamus and pons. Lobar haemorrhage in contrast is thought to be, primarily caused by cerebral amyloid angiopathy.
Christopher J Taylor BSc (Hons) MBBS MRCP FRCA FFICM is a Consultant in Neuroanaesthesia and Neurocritcal Care at the National Hospital for Neurology and Neurosurgery, London, UK. Conflicts of interest: none declared.
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Ó 2019 Published by Elsevier Ltd.
Please cite this article as: Taylor CJ, The management of spontaneous primary intracerebral haemorrhage, Anaesthesia and intensive care medicine, https://doi.org/10.1016/j.mpaic.2019.10.021
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Investigations
Deep haemorrhage In putaminal haemorrhage (Figure 1) there is contralateral hemiparesis and conjugate deviation of the eyes towards the side of the haematoma. If the mass effect becomes critical then signs of herniation ensue and rupture into the ventricle may occur (Figure 2).
Standard urgent blood tests including FBC, U&Es, glucose, LFTs, ABG, clotting and group and save should be performed as well as chest radiograph and ECG. Specialized tests to assess platelet function or near patient testing of coagulation such as TEG or RoTEC can be of use if available. Acutely, a non-contrast cranial computed tomography (CT) scan is essential to distinguish infarction from haemorrhage or reveal mimics of the stroke syndrome such as tumour or subdural haematoma. Haemorrhages seen on magnetic resonance imaging (MRI) show complex changes depending on the image sequence; however, signal loss on susceptibility-weighted MRI is more specific and sensitive to new and old haemorrhages than the older MRI sequences. In appropriate patients it is necessary to exclude an aneurysm or underlying vascular malformations using contrast enhanced CT angiography (CTA) or magnetic resonance angiography (MRA), with greater than 90% sensitivity. These may, however miss small lesions and digital subtraction angiography (DSA) is required in some cases.
Lobar haemorrhage In the frontal lobe, ipsilateral eye deviation, contralateral hemiparesis and/or hemisensory loss occurs, associated with dysphasia when the lesion is within the dominant hemisphere. Parietal lobe haemorrhage causes hemisensory loss and neglect/ inattention syndromes. Bleeding into the dominant temporal lobe results in a fluent dysphasia with poor comprehension. Infratentorial haemorrhage Pontine haemorrhage (Figure 3) causes coma associated with pinpoint pupils, loss of horizontal eye movements and quadriparesis. Hyperpyrexia and irregular respiratory patterns ensue. Although a large haematoma here is often fatal, the outcome may be good in some patients. Cerebellar haemorrhage may result in secondary fatal brainstem compression and hydrocephalus. The usual picture is of acute headache and vomiting with unilateral ataxia and ipsilateral hypotonia.
Management (Box 1) According to the AHA/ASA guidelines ICH is a medical emergency. General supportive management issues are just as important as in ischaemic stroke. The initial assessment, monitoring and management of ICH patients should take place in a resuscitation room and then ideally, progress on to a critical care setting or a dedicated stroke unit with physician and nursing neuroscience acute care expertise. Standardized neurological assessment is essential to determine baseline severity. The National Institutes of Health stroke scale (NIHSS), should be determined and documented if the patient is awake or drowsy, or Glagow Coma Scale (GCS), if the patient is obtunded or comatose. Rapid diagnosis and attentive management of patients is vital because deterioration is common; up to 20% of patients will experience a decrease of 2 or more in their GCS within the first few hours after ictus. The primary objective is an ABCD initial assessment and stabilization of the patient, optimization of physiology (maintaining cerebral perfusion and oxygenation) in order to prevent secondary cerebral insults similar to brain injury foundation guidelines. Airway management is essential if GCS <8 or conscious level is fluctuant or the airway is compromised. Ensuring adequate ventilation once the airway is secured to control CO2 between 4.5 and 5 kPa and adequate oxygenation to achieve PO2 >13 kPa. Keeping the head elevated by 30 and avoiding anything that will impede cerebral venous drainage will help control ICP. In patients with severe ICH, optimal sedation with infusions of an opioid such as fentanyl and propofol help to control cerebral perfusion pressure, cerebral vascular tone and metabolic rate and, in turn, intracranial pressure. Maintaining normothermia, normoglycaemia, normovolaemia and haemodynamic stability and intracranial pressure are vital to prevent poor outcome. Frequent hourly neurological examination is required in order to identify any neurological deterioration requiring further investigation or management. Once physiological stability has been established it is essential to review the medical history and identify appropriate risk factors: previous stroke or ICH, hypertension, diabetes mellitus,
Intraventricular haemorrhage Intraventricular haemorrhage (Figure 2) mimics subarachnoid haemorrhage (SAH) with headache, vomiting, neck stiffness and depression of consciousness. There may be associated pyramidal signs, particularly if associated with a parenchymal haematoma. There is an increased risk of developing secondary hydrocephalus requiring CSF drainage.
Figure 1 CT scan showing extensive ganglionic ICH.
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Ó 2019 Published by Elsevier Ltd.
Please cite this article as: Taylor CJ, The management of spontaneous primary intracerebral haemorrhage, Anaesthesia and intensive care medicine, https://doi.org/10.1016/j.mpaic.2019.10.021
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(clopidogrel, prasugrel, non-steroidal anti-inflammatory agents actions (dipyridamole) should be stopped and corrected. Blood pressure Elevated blood pressure (BP) is a common occurrence in acute ICH and a number of factors have been identified including stress, pain increased ICP and premorbid acute or persistent undiagnosed elevations in blood pressure. Higher systolic blood pressure is associated with greater haematoma expansion, neurological deterioration and worse outcome: death or neurological dependency. Early intensive lowering of blood pressure was shown to be safe in the second INTERACT trial. Secondary analyses suggested that this might improve outcome but the effects of rapid blood pressure reduction on cerebral autoregulation and perihaematoma ischaemia remain uncertain. Following on from the randomized clinical ATACH 2 trial 2018, many critical care units (including our own) have adjusted their systolic blood pressure target for the first week following ICH to aim for a systolic value less than 140 mmHg which is now thought to be a relatively safe target. There will of course be exceptions to the rule, such as chronic hypertensive individuals who require higher targeted renal, cardiac and cerebral perfusion pressures even within the first week and blood pressure target adaptations may need to be made in certain circumstances. After the first week, blood pressure targets can then be ‘relaxed’ according to the individual needs. Acutely, blood pressure is controlled using sedative agents in intubated and ventilated patients, but intravenous agents such a beta blockers (labetalol), calcium channel blockers (nicardipine) or vasodilators (hydralazine) can be very helpful in achieving blood pressure control until regular enteral antihypertensives have been commenced and established. Intracranial pressure should be kept <20 mmHg and cerebral perfusion >60 mmHg (see Box 1).
Figure 2 CT scan showing caudate haemorrhage, which has ruptured into the ventricle.
Correction of anticoagulation Haematoma expansion is a critical determinant of mortality and outcome. Anticoagulant-related haematomas often present as slowly evolving lesions. It is essential, even if they are small at initial imaging, to reverse warfarin immediately using vitamin K. The use of fresh frozen plasma (FFP) increases the risk of transfusion related lung injury so prothrombin complex concentrates (PCC) are now preferable but costly. With increasing use of target-specific oral anticoagulants, improved point of care testing (e.g. TEG haemostasis analysis and platelet function tests) help direct most appropriate reversal. For patients with prosthetic valves the riskebenefit ratio is much in favour of anticoagulation reversal for a period of 2 weeks, after which the rebleeding rate is considerably lower. Newer factor 10 inhibitor anticoagulants such as rivaroxaban, apixaban or dabigatran may have a better safety profile but do not have specific antidotes. Initial trials of recombinant activated factor VII showed that this pro-coagulant appeared to reduce haematoma size and improves outcome when given within 4 hours of onset; however, phase IIb/IIIa studies have been negative. Haematological advice should be sought in these circumstances, but treatment with prothrombin complex concentrates in association with antifibrinolytics such as tranexamic acid can be of use and usually recommended.
Figure 3 CT scan showing extensive pontine haemorrhage.
renal impairment, cardiac history, alcohol use and smoking. Medications: anticoagulants drugs, antiplatelet agents, antihypertensive medications, stimulant and sympathomimetic illicit dugs misuse such as cocaine. Any recent trauma or surgery: carotid endarterectomy/stent, because ICH may be related to hypertension after such procedures. A history of dementia may suggest a cause of amyloid angiopathy or identifying a history of liver disease and/or cancer may link to an associated coagulopathy. A history of epilepsy or any documented seizures at presentation is important in targeting appropriate investigations such as EEG and considering antiepileptic medications. Medical treatment is aimed at correcting any underlying systemic disorder such as severe hypertension or coagulopathy, as well as preventing or limiting secondary complications such as pulmonary emboli, myocardial infarction, and pneumonia. Warfarin, aspirin or any other medication with antithrombotic (e.g. rivaroxaban, apixaban or fondaparinux) or antiplatelet actions
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Please cite this article as: Taylor CJ, The management of spontaneous primary intracerebral haemorrhage, Anaesthesia and intensive care medicine, https://doi.org/10.1016/j.mpaic.2019.10.021
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Temperature management Fever worsens outcome in experimental models of brain injury. Fever is a common finding in ICH patients especially in those who have deep, Intraventricular or infratentorial haemorrhage. Recent observational studies have linked fever (>37 C) within the first 72 hours post ICH as an independent factor associated with poor functional outcome.3 It is therefore wise to control body temperature <37 C and external cooling devices can be used to achieve this.
ICU management of intracerebral haemorrhage (ICH) C C C
Airway management Investigation and monitoring Blood pressure (BP) control e controversial Systolic BP (SBP) <140 mmHg for first week post ictus. Achieved using continuous sedation infusions of fentanyl/ propofol and antihypertensive (labetalol or hydralazine) as required once ICP bolt in situ consider aiming for CPP >60 mmHg
C
Neurosurgical intervention The role of acute neurosurgical treatment, in particular, craniotomy and haematoma evacuation in spontaneous ICH still remains controversial. The theoretical rationale focuses on haematoma evacuation and its perceived beneficial effect in reducing ICP, preventing herniation and local effects of haematoma on surrounding brain tissue in respect to cellular toxicity. Randomized trials such as the STICH II multicentre trial comparing early surgery, clot evacuation (within 12 hours) to conservative management in awake patients with supratentorial ICH have not demonstrated a clear benefit for surgical intervention. The latest recommendations are that supratentorial haematoma evacuation and decompressive craniectomy in deteriorating patients might be considered as a life-saving measure in specific cases who are in coma with a high ICP and/or who have large haematomas with significant midline shift. However, in contrast to supratentorial haematomas, with respect to infratentorial haematomas, because of the limited space available within the posterior fossa, deterioration can occur rapidly in patients with life-threatening cerebellar haematomas large enough (>3 cm) to cause brainstem compression and hydrocephalus and several non-randomized studies have shown better outcome with surgical clot evacuation and decompression compared to conservative management. Deep-seated basal ganglia haematomas are not usually evacuated because the associated morbidity is significant. Urgent CSF drainage with the insertion of emergency external ventricular drains to treat secondary hydrocephalus, especially in IVH is a life saving neurosurgical intervention and in association with intracranial bolt insertion can to help manage raised intracranial hypertension in the ICU setting.
Haemostatic therapy Reversal of anticoagulation (IV vitamin K, PCC or coagulation factors) Recombinant factor VII (rFVII) is unproven
C
Raised intracranial pressure (ICP)/cerebral oedema Positioning (head up >30_) remove all restrictive ties Anaesthesia and sedation ICP monitor (if coma, mass effect, Intraventricular extension, hydrocephalus) Pressor agents to optimize cerebral perfusion pressure (CPP) Osmotherapy (20% mannitol 0.5e1.0 g/kg intravenous infusion (IVI)) or hypertonic saline 2.8% controlled ventilation to achieve (PaO2 >13 KPa & PaCO2 4.5e5.0 KPa) Maintain Normothermia Surgical intervention (ventricular drainage or definitive intervention)
C
Control of: Seizures (prophylactic antiepileptic drugs not indicated) Maintain normoglycaemia (aim for glucose 5.5e10 mmol/L) Institute early feeding (nasogastric tube) DVT prophylaxis (stockings, pneumatic compression, LMWH consideration 48 hours after ICH)
C
Surgical intervention (controversial) EXTRAVENTRICULAR drainage for hydrocephalus Craniotomy and clot evacuation (e.g. cerebellar haematoma) Endoscopic guidance techniques Hemicraniectomy
Box 1
Grading of severity and prognosis of ICH
Plasma glucose Plasma glucose should be monitored regularly and both hyperglycaemia and hypoglycaemia should be avoided because they are linked to poor outcome. A randomized trial showed improved outcomes with tight control (4e6 mmol/l) using insulin infusions in mainly surgical critical care patients. However more recent studies in stroke patients using ‘tight glucose control’ have demonstrated an increased incidence of systemic and cerebral hypoglycaemic events and better outcomes are seen in stroke patients with more ‘relaxed’ targets. At present, the optimal management of hyperglycaemia in ICH and target glucose level remains to be clarified, our critical care unit protocol targets plasma glucose to between 7 and 12 mmol/l.
The prognosis following ICH depends primarily on the location and the size of the haematoma. There are five major risk factors that have been identified that are linked with poor outcome following ICH. The ICH score was first proposed by Hemphill et al. and uses a combination of these five factors to give an overall score and prognosis (Table 1). Firstly, the presenting GCS of less than 8 is strongly linked with poor outcome. In addition, the size of the bleed; the volume of blood on the initial non-contrast CT image has a strong independent association with outcome. A haematoma volume of 30 ml represents a cut-off point for increased mortality4 and worse functional outcome.5 When combined together GCS and volume of haematoma are powerful predictors: patients with ICH volume >60 ml on initial CT image and a GCS >8 have a predicted 30-day mortality >90%.
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Ó 2019 Published by Elsevier Ltd.
Please cite this article as: Taylor CJ, The management of spontaneous primary intracerebral haemorrhage, Anaesthesia and intensive care medicine, https://doi.org/10.1016/j.mpaic.2019.10.021
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The development and severity of post-haemorrhagic complications such as early haematoma expansion as indicated by a ‘spot sign’ on CTH (Figure 4), cerebral oedema, hydrocephalus and raised intracranial pressure together with the development of systemic complications such as pulmonary embolus, MI, pneumonia as well as deranged serum glucose and fibrinogen have all been linked with poor outcome following ICH. Improvement following haemorrhage tends to be more delayed than following infarction and eventual recovery may be good following resolution of the haematoma. The overall ICU mortality for ICH in the UK is 42%, but the acute hospital mortality rises to 62%.
ICH score Component GCS score 3e4 5e12 13e15 ICH volume, cm3 30 <30 IVH Yes No Infratentorial origin of ICH Yes No Age, years 80 <80
ICH score point
2 1 0 1 0 1 0
Prevention of recurrent ICH Patients with ICH are at high risk of a recurrent bleed as well as other major vascular disease. The cumulative risk of ICH recurrence is between 1 and 5% per year, although the highest risk is within the first year after the initial event, particularly in patients with lobar ICH. Hypertension, older age and location of the initial haemorrhage (deep versus lobar) are noted to be important risk factors for ICH recurrence. High blood pressure is associated with an increase in the recurrence of both deep and lobar haemorrhages. Increased risk in the elderly is attributed to higher prevalence of cerebral amyloid angiopathy.
1 0 1 0
Table 1
Furthermore, the presence of intraventricular haemorrhage (IVH) is associated with the development of secondary hydrocephalus and can potentially double the probability of a poor outcome. In addition, the haematoma location is another important factor that affects outcome and treatment. Infratentorial bleeds in the cerebellum are associated with a poorer outcome. The most common locations of hypertensive bleeds are deeply located basal ganglia (caudate nucleus and putamen), thalamus, midbrain, pons or cerebellum where as lobar haemorrhage are often associated with structural changes such as amyloid angiopathy. Finally, age greater than 80 years significantly increase the likelihood of poor outcome and death.
Conclusion Spontaneous primary ICH is a common cause of stroke with a high incidence of morbidity and mortality. Management focuses on the rapid diagnosis, general supportive care preventing haematoma expansion and secondary brain injury by controlling blood pressure and intracranial pressure (ICP), the reversal of anticoagulation and, where indicated, neurosurgical intervention. The prognosis for functional recovery depends upon the location of haemorrhage, size of the haematoma, level of consciousness and patient age. A REFERENCES 1 Feigin VL, Lawes CM, Bennett DA, et al. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol 2009; 8: 355e69. https://doi.org/10.1016/S1474-4422(09)70025-0. 2 Asch CJ, Luitse MJ, Rinkel GJ, et al. Incidence, case fatality and functional outcome of intracerebral haemorrhage over time, according to age, sex and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 2010; 9: 167e76. 3 Rincon F, Lyden P, Mayer SA. Relationship between temperature, hematoma growth and functional outcome after intracerebral haemorrhage. Neurocritical Care 2013; 18: 45e53. 4 Hemphill JC, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracranial hemorrhage. Stroke 2001; 32: 891e7. 5 Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of intraccerebral hemorrhage. A powerful and easy-to-use predictor of 30 day mortality. Stroke 1993; 24: 987e93.
Figure 4 CT scan showing extensive ICH with red arrow highlighting a ‘spot sign’: early re-haemorrhage.
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Ó 2019 Published by Elsevier Ltd.
Please cite this article as: Taylor CJ, The management of spontaneous primary intracerebral haemorrhage, Anaesthesia and intensive care medicine, https://doi.org/10.1016/j.mpaic.2019.10.021
The management of spontaneous primary intracerebral haemorrhage
Learning objectives After reading this article, you should be able to: C describe the initial assessment and management of acute intracerebral haemorrhage C identify the causes of Intracerebral haemorrhage C identify the prognostic factors in intracerebral haemorrhage
Christopher J Taylor
Abstract
Causes and risk factors
Intracerebral haemorrhage (ICH) accounts for around 10e20% of all strokes and results from a variety of disorders. ICH is more likely to result in death or major disability than ischaemic stroke or subarachnoid haemorrhage. Rapid imaging allows early diagnosis and characterization of the localization and severity of the haemorrhage. Patients with significant acute ICH should be managed in a critical care unit. Treatment entails general supportive care, control of blood pressure and intracranial pressure, prevention of haematoma expansion and, where indicated, neurosurgical intervention. In those patients whose bleed extends into the ventricular system or who have infratentorial bleeds are at increased risk of associated hydrocephalus, rapidly increasing intracranial pressure requiring urgent CSF drainage. The 30-day mortality from intracerebral haemorrhage ranges from 35 e52%. Among survivors, the prognosis for functional recovery depends upon the location of haemorrhage, size of the haematoma, level of consciousness, the patient’s age, and overall medical condition.
Primary ICH is strongly associated with a number of risk factors or structural abnormalities, which include: hypertension e present in 40e60% of patients cerebral amyloid angiopathy (CAA). medication: anticoagulants coagulopathies smoking sporadic cerebral amyloid angiopathy drugs of abuse (alcohol but, particularly, cocaine and amphetamine) vasculitis diabetes mellitus. Hypertension is the single most important risk factor for primary ICH. Multiple meta-analyses have suggested hypertension >160/90 increases the risk of intracerebral haemorrhage by more than nine times. After hypertension, the second most important risk factor is thought to be due to cerebral amyloid angiopathy: the accumulation of beta amyloid within the media and adventitia of cerebral blood vessels disrupting their structure increasing the chance of blood leakage and rupture. Medication in the form of anticoagulants (e.g. warfarin), antiplatelets drugs (e.g. aspirin and clopidogrel) and newer agents (e.g. factor 10 inhibitors such as rivaroxaban) all increase the risk of ICH; however, the benefits of these drugs far outweigh the risks associated with their use.
Keywords Intracerebral haemorrhage; intracranial haemorrhage Royal College of Anaesthetists CPD Matrix: 2F01
Intracranial haemorrhage Intracranial haemorrhage may be intracerebral, subarachnoid, subdural or extradural. Approximately 10e20% of stroke is caused by intracerebral haemorrhage (ICH) and is the second most common form of stroke after ischaemic stroke with an annual incidence of 20e25/100,000 of the UK population. The incidence increases significantly after the age of 55 years and doubles with each decade to the age of 80.1,2 Intracerebral haemorrhage can occur as a complication of a pre-existing brain lesion, such as a tumour, recent infarct or vascular malformation and is referred to as secondary intracerebral haemorrhage. This article will only focus on ‘primary’ spontaneous intracerebral haemorrhage, that is, Intracerebral haemorrhage or bleeding into the brain parenchyma in the absence of a clear underlying lesion. The article will review the potential causes, risk factors, presentation, investigations, management and prognosis of this important condition.
Clinical presentation and syndromes of intracranial haemorrhage Primary ICH occurs following the rupture of a blood vessel within the brain parenchyma with the sudden development of haematoma of variable size that slowly enlarges over hours or days, especially in patients on anticoagulants, leading to progressive focal neurological deficit and deterioration in conscious level secondary to mass effect. Headache, vomiting and a decreased level of consciousness develop if the haematoma becomes sufficiently large. Seizures in the first days after ICH occur in <30%; the development of stupor or coma is an ominous sign. Neurological signs vary depending upon the location of the haemorrhage. Deep haemorrhage especially into the putamen is especially associated with hypertension and occurs in approximately 35%, subcortex in 30% and, less commonly, into the cerebellum, thalamus and pons. Lobar haemorrhage in contrast is thought to be, primarily caused by cerebral amyloid angiopathy.
Christopher J Taylor BSc (Hons) MBBS MRCP FRCA FFICM is a Consultant in Neuroanaesthesia and Neurocritcal Care at the National Hospital for Neurology and Neurosurgery, London, UK. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE xxx:xxx
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Ó 2019 Published by Elsevier Ltd.
Please cite this article as: Taylor CJ, The management of spontaneous primary intracerebral haemorrhage, Anaesthesia and intensive care medicine, https://doi.org/10.1016/j.mpaic.2019.10.021
NEUROINTENSIVE CARE
Investigations
Deep haemorrhage In putaminal haemorrhage (Figure 1) there is contralateral hemiparesis and conjugate deviation of the eyes towards the side of the haematoma. If the mass effect becomes critical then signs of herniation ensue and rupture into the ventricle may occur (Figure 2).
Standard urgent blood tests including FBC, U&Es, glucose, LFTs, ABG, clotting and group and save should be performed as well as chest radiograph and ECG. Specialized tests to assess platelet function or near patient testing of coagulation such as TEG or RoTEC can be of use if available. Acutely, a non-contrast cranial computed tomography (CT) scan is essential to distinguish infarction from haemorrhage or reveal mimics of the stroke syndrome such as tumour or subdural haematoma. Haemorrhages seen on magnetic resonance imaging (MRI) show complex changes depending on the image sequence; however, signal loss on susceptibility-weighted MRI is more specific and sensitive to new and old haemorrhages than the older MRI sequences. In appropriate patients it is necessary to exclude an aneurysm or underlying vascular malformations using contrast enhanced CT angiography (CTA) or magnetic resonance angiography (MRA), with greater than 90% sensitivity. These may, however miss small lesions and digital subtraction angiography (DSA) is required in some cases.
Lobar haemorrhage In the frontal lobe, ipsilateral eye deviation, contralateral hemiparesis and/or hemisensory loss occurs, associated with dysphasia when the lesion is within the dominant hemisphere. Parietal lobe haemorrhage causes hemisensory loss and neglect/ inattention syndromes. Bleeding into the dominant temporal lobe results in a fluent dysphasia with poor comprehension. Infratentorial haemorrhage Pontine haemorrhage (Figure 3) causes coma associated with pinpoint pupils, loss of horizontal eye movements and quadriparesis. Hyperpyrexia and irregular respiratory patterns ensue. Although a large haematoma here is often fatal, the outcome may be good in some patients. Cerebellar haemorrhage may result in secondary fatal brainstem compression and hydrocephalus. The usual picture is of acute headache and vomiting with unilateral ataxia and ipsilateral hypotonia.
Management (Box 1) According to the AHA/ASA guidelines ICH is a medical emergency. General supportive management issues are just as important as in ischaemic stroke. The initial assessment, monitoring and management of ICH patients should take place in a resuscitation room and then ideally, progress on to a critical care setting or a dedicated stroke unit with physician and nursing neuroscience acute care expertise. Standardized neurological assessment is essential to determine baseline severity. The National Institutes of Health stroke scale (NIHSS), should be determined and documented if the patient is awake or drowsy, or Glagow Coma Scale (GCS), if the patient is obtunded or comatose. Rapid diagnosis and attentive management of patients is vital because deterioration is common; up to 20% of patients will experience a decrease of 2 or more in their GCS within the first few hours after ictus. The primary objective is an ABCD initial assessment and stabilization of the patient, optimization of physiology (maintaining cerebral perfusion and oxygenation) in order to prevent secondary cerebral insults similar to brain injury foundation guidelines. Airway management is essential if GCS <8 or conscious level is fluctuant or the airway is compromised. Ensuring adequate ventilation once the airway is secured to control CO2 between 4.5 and 5 kPa and adequate oxygenation to achieve PO2 >13 kPa. Keeping the head elevated by 30 and avoiding anything that will impede cerebral venous drainage will help control ICP. In patients with severe ICH, optimal sedation with infusions of an opioid such as fentanyl and propofol help to control cerebral perfusion pressure, cerebral vascular tone and metabolic rate and, in turn, intracranial pressure. Maintaining normothermia, normoglycaemia, normovolaemia and haemodynamic stability and intracranial pressure are vital to prevent poor outcome. Frequent hourly neurological examination is required in order to identify any neurological deterioration requiring further investigation or management. Once physiological stability has been established it is essential to review the medical history and identify appropriate risk factors: previous stroke or ICH, hypertension, diabetes mellitus,
Intraventricular haemorrhage Intraventricular haemorrhage (Figure 2) mimics subarachnoid haemorrhage (SAH) with headache, vomiting, neck stiffness and depression of consciousness. There may be associated pyramidal signs, particularly if associated with a parenchymal haematoma. There is an increased risk of developing secondary hydrocephalus requiring CSF drainage.
Figure 1 CT scan showing extensive ganglionic ICH.
ANAESTHESIA AND INTENSIVE CARE MEDICINE xxx:xxx
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Ó 2019 Published by Elsevier Ltd.
Please cite this article as: Taylor CJ, The management of spontaneous primary intracerebral haemorrhage, Anaesthesia and intensive care medicine, https://doi.org/10.1016/j.mpaic.2019.10.021
NEUROINTENSIVE CARE
(clopidogrel, prasugrel, non-steroidal anti-inflammatory agents actions (dipyridamole) should be stopped and corrected. Blood pressure Elevated blood pressure (BP) is a common occurrence in acute ICH and a number of factors have been identified including stress, pain increased ICP and premorbid acute or persistent undiagnosed elevations in blood pressure. Higher systolic blood pressure is associated with greater haematoma expansion, neurological deterioration and worse outcome: death or neurological dependency. Early intensive lowering of blood pressure was shown to be safe in the second INTERACT trial. Secondary analyses suggested that this might improve outcome but the effects of rapid blood pressure reduction on cerebral autoregulation and perihaematoma ischaemia remain uncertain. Following on from the randomized clinical ATACH 2 trial 2018, many critical care units (including our own) have adjusted their systolic blood pressure target for the first week following ICH to aim for a systolic value less than 140 mmHg which is now thought to be a relatively safe target. There will of course be exceptions to the rule, such as chronic hypertensive individuals who require higher targeted renal, cardiac and cerebral perfusion pressures even within the first week and blood pressure target adaptations may need to be made in certain circumstances. After the first week, blood pressure targets can then be ‘relaxed’ according to the individual needs. Acutely, blood pressure is controlled using sedative agents in intubated and ventilated patients, but intravenous agents such a beta blockers (labetalol), calcium channel blockers (nicardipine) or vasodilators (hydralazine) can be very helpful in achieving blood pressure control until regular enteral antihypertensives have been commenced and established. Intracranial pressure should be kept <20 mmHg and cerebral perfusion >60 mmHg (see Box 1).
Figure 2 CT scan showing caudate haemorrhage, which has ruptured into the ventricle.
Correction of anticoagulation Haematoma expansion is a critical determinant of mortality and outcome. Anticoagulant-related haematomas often present as slowly evolving lesions. It is essential, even if they are small at initial imaging, to reverse warfarin immediately using vitamin K. The use of fresh frozen plasma (FFP) increases the risk of transfusion related lung injury so prothrombin complex concentrates (PCC) are now preferable but costly. With increasing use of target-specific oral anticoagulants, improved point of care testing (e.g. TEG haemostasis analysis and platelet function tests) help direct most appropriate reversal. For patients with prosthetic valves the riskebenefit ratio is much in favour of anticoagulation reversal for a period of 2 weeks, after which the rebleeding rate is considerably lower. Newer factor 10 inhibitor anticoagulants such as rivaroxaban, apixaban or dabigatran may have a better safety profile but do not have specific antidotes. Initial trials of recombinant activated factor VII showed that this pro-coagulant appeared to reduce haematoma size and improves outcome when given within 4 hours of onset; however, phase IIb/IIIa studies have been negative. Haematological advice should be sought in these circumstances, but treatment with prothrombin complex concentrates in association with antifibrinolytics such as tranexamic acid can be of use and usually recommended.
Figure 3 CT scan showing extensive pontine haemorrhage.
renal impairment, cardiac history, alcohol use and smoking. Medications: anticoagulants drugs, antiplatelet agents, antihypertensive medications, stimulant and sympathomimetic illicit dugs misuse such as cocaine. Any recent trauma or surgery: carotid endarterectomy/stent, because ICH may be related to hypertension after such procedures. A history of dementia may suggest a cause of amyloid angiopathy or identifying a history of liver disease and/or cancer may link to an associated coagulopathy. A history of epilepsy or any documented seizures at presentation is important in targeting appropriate investigations such as EEG and considering antiepileptic medications. Medical treatment is aimed at correcting any underlying systemic disorder such as severe hypertension or coagulopathy, as well as preventing or limiting secondary complications such as pulmonary emboli, myocardial infarction, and pneumonia. Warfarin, aspirin or any other medication with antithrombotic (e.g. rivaroxaban, apixaban or fondaparinux) or antiplatelet actions
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Temperature management Fever worsens outcome in experimental models of brain injury. Fever is a common finding in ICH patients especially in those who have deep, Intraventricular or infratentorial haemorrhage. Recent observational studies have linked fever (>37 C) within the first 72 hours post ICH as an independent factor associated with poor functional outcome.3 It is therefore wise to control body temperature <37 C and external cooling devices can be used to achieve this.
ICU management of intracerebral haemorrhage (ICH) C C C
Airway management Investigation and monitoring Blood pressure (BP) control e controversial Systolic BP (SBP) <140 mmHg for first week post ictus. Achieved using continuous sedation infusions of fentanyl/ propofol and antihypertensive (labetalol or hydralazine) as required once ICP bolt in situ consider aiming for CPP >60 mmHg
C
Neurosurgical intervention The role of acute neurosurgical treatment, in particular, craniotomy and haematoma evacuation in spontaneous ICH still remains controversial. The theoretical rationale focuses on haematoma evacuation and its perceived beneficial effect in reducing ICP, preventing herniation and local effects of haematoma on surrounding brain tissue in respect to cellular toxicity. Randomized trials such as the STICH II multicentre trial comparing early surgery, clot evacuation (within 12 hours) to conservative management in awake patients with supratentorial ICH have not demonstrated a clear benefit for surgical intervention. The latest recommendations are that supratentorial haematoma evacuation and decompressive craniectomy in deteriorating patients might be considered as a life-saving measure in specific cases who are in coma with a high ICP and/or who have large haematomas with significant midline shift. However, in contrast to supratentorial haematomas, with respect to infratentorial haematomas, because of the limited space available within the posterior fossa, deterioration can occur rapidly in patients with life-threatening cerebellar haematomas large enough (>3 cm) to cause brainstem compression and hydrocephalus and several non-randomized studies have shown better outcome with surgical clot evacuation and decompression compared to conservative management. Deep-seated basal ganglia haematomas are not usually evacuated because the associated morbidity is significant. Urgent CSF drainage with the insertion of emergency external ventricular drains to treat secondary hydrocephalus, especially in IVH is a life saving neurosurgical intervention and in association with intracranial bolt insertion can to help manage raised intracranial hypertension in the ICU setting.
Haemostatic therapy Reversal of anticoagulation (IV vitamin K, PCC or coagulation factors) Recombinant factor VII (rFVII) is unproven
C
Raised intracranial pressure (ICP)/cerebral oedema Positioning (head up >30_) remove all restrictive ties Anaesthesia and sedation ICP monitor (if coma, mass effect, Intraventricular extension, hydrocephalus) Pressor agents to optimize cerebral perfusion pressure (CPP) Osmotherapy (20% mannitol 0.5e1.0 g/kg intravenous infusion (IVI)) or hypertonic saline 2.8% controlled ventilation to achieve (PaO2 >13 KPa & PaCO2 4.5e5.0 KPa) Maintain Normothermia Surgical intervention (ventricular drainage or definitive intervention)
C
Control of: Seizures (prophylactic antiepileptic drugs not indicated) Maintain normoglycaemia (aim for glucose 5.5e10 mmol/L) Institute early feeding (nasogastric tube) DVT prophylaxis (stockings, pneumatic compression, LMWH consideration 48 hours after ICH)
C
Surgical intervention (controversial) EXTRAVENTRICULAR drainage for hydrocephalus Craniotomy and clot evacuation (e.g. cerebellar haematoma) Endoscopic guidance techniques Hemicraniectomy
Box 1
Grading of severity and prognosis of ICH
Plasma glucose Plasma glucose should be monitored regularly and both hyperglycaemia and hypoglycaemia should be avoided because they are linked to poor outcome. A randomized trial showed improved outcomes with tight control (4e6 mmol/l) using insulin infusions in mainly surgical critical care patients. However more recent studies in stroke patients using ‘tight glucose control’ have demonstrated an increased incidence of systemic and cerebral hypoglycaemic events and better outcomes are seen in stroke patients with more ‘relaxed’ targets. At present, the optimal management of hyperglycaemia in ICH and target glucose level remains to be clarified, our critical care unit protocol targets plasma glucose to between 7 and 12 mmol/l.
The prognosis following ICH depends primarily on the location and the size of the haematoma. There are five major risk factors that have been identified that are linked with poor outcome following ICH. The ICH score was first proposed by Hemphill et al. and uses a combination of these five factors to give an overall score and prognosis (Table 1). Firstly, the presenting GCS of less than 8 is strongly linked with poor outcome. In addition, the size of the bleed; the volume of blood on the initial non-contrast CT image has a strong independent association with outcome. A haematoma volume of 30 ml represents a cut-off point for increased mortality4 and worse functional outcome.5 When combined together GCS and volume of haematoma are powerful predictors: patients with ICH volume >60 ml on initial CT image and a GCS >8 have a predicted 30-day mortality >90%.
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The development and severity of post-haemorrhagic complications such as early haematoma expansion as indicated by a ‘spot sign’ on CTH (Figure 4), cerebral oedema, hydrocephalus and raised intracranial pressure together with the development of systemic complications such as pulmonary embolus, MI, pneumonia as well as deranged serum glucose and fibrinogen have all been linked with poor outcome following ICH. Improvement following haemorrhage tends to be more delayed than following infarction and eventual recovery may be good following resolution of the haematoma. The overall ICU mortality for ICH in the UK is 42%, but the acute hospital mortality rises to 62%.
ICH score Component GCS score 3e4 5e12 13e15 ICH volume, cm3 30 <30 IVH Yes No Infratentorial origin of ICH Yes No Age, years 80 <80
ICH score point
2 1 0 1 0 1 0
Prevention of recurrent ICH Patients with ICH are at high risk of a recurrent bleed as well as other major vascular disease. The cumulative risk of ICH recurrence is between 1 and 5% per year, although the highest risk is within the first year after the initial event, particularly in patients with lobar ICH. Hypertension, older age and location of the initial haemorrhage (deep versus lobar) are noted to be important risk factors for ICH recurrence. High blood pressure is associated with an increase in the recurrence of both deep and lobar haemorrhages. Increased risk in the elderly is attributed to higher prevalence of cerebral amyloid angiopathy.
1 0 1 0
Table 1
Furthermore, the presence of intraventricular haemorrhage (IVH) is associated with the development of secondary hydrocephalus and can potentially double the probability of a poor outcome. In addition, the haematoma location is another important factor that affects outcome and treatment. Infratentorial bleeds in the cerebellum are associated with a poorer outcome. The most common locations of hypertensive bleeds are deeply located basal ganglia (caudate nucleus and putamen), thalamus, midbrain, pons or cerebellum where as lobar haemorrhage are often associated with structural changes such as amyloid angiopathy. Finally, age greater than 80 years significantly increase the likelihood of poor outcome and death.
Conclusion Spontaneous primary ICH is a common cause of stroke with a high incidence of morbidity and mortality. Management focuses on the rapid diagnosis, general supportive care preventing haematoma expansion and secondary brain injury by controlling blood pressure and intracranial pressure (ICP), the reversal of anticoagulation and, where indicated, neurosurgical intervention. The prognosis for functional recovery depends upon the location of haemorrhage, size of the haematoma, level of consciousness and patient age. A REFERENCES 1 Feigin VL, Lawes CM, Bennett DA, et al. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol 2009; 8: 355e69. https://doi.org/10.1016/S1474-4422(09)70025-0. 2 Asch CJ, Luitse MJ, Rinkel GJ, et al. Incidence, case fatality and functional outcome of intracerebral haemorrhage over time, according to age, sex and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 2010; 9: 167e76. 3 Rincon F, Lyden P, Mayer SA. Relationship between temperature, hematoma growth and functional outcome after intracerebral haemorrhage. Neurocritical Care 2013; 18: 45e53. 4 Hemphill JC, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracranial hemorrhage. Stroke 2001; 32: 891e7. 5 Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of intraccerebral hemorrhage. A powerful and easy-to-use predictor of 30 day mortality. Stroke 1993; 24: 987e93.
Figure 4 CT scan showing extensive ICH with red arrow highlighting a ‘spot sign’: early re-haemorrhage.
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Please cite this article as: Taylor CJ, The management of spontaneous primary intracerebral haemorrhage, Anaesthesia and intensive care medicine, https://doi.org/10.1016/j.mpaic.2019.10.021