Neurología.

2013;28(4):236—249

NEUROLOGÍA
www.elsevier.es/neurologia

REVIEW ARTICLE

Clinical practice guidelines in intracerebral haemorrhage夽

M. Rodríguez-Yáñez, M. Castellanos, M.M. Freijo, J.C. López Fernández,
J. Martí-Fàbregas, F. Nombela, P. Simal, J. Castillo∗ , E. Díez-Tejedor (Coordinator),
B. Fuentes (Secretaria), M. Alonso de Leciñana, J. Álvarez-Sabin, J. Arenillas,
S. Calleja, I. Casado, A. Dávalos, F. Díaz-Otero, J.A. Egido, J. Gállego, A. García Pastor,
A. Gil-Núñez, F. Gilo, P. Irimia, A. Lago, J. Maestre, J. Masjuan, P. Martínez-Sánchez,
E. Martínez-Vila, C. Molina, A. Morales, F. Purroy, M. Ribó, J. Roquer, F. Rubio,
T. Segura, J. Serena, J. Tejada, J. Vivancos♦ , representing the ad hoc committee of the
SEN Study Group for Cerebrovascular Diseases:

Received 23 February 2011; accepted 6 March 2011

Available online 4 May 2013

KEYWORDS Abstract Intracerebral haemorrhage accounts for 10% to 15% of all strokes, however it has a
Intracerebral poor prognosis with higher rates of morbidity and mortality. Neurological deterioration is often
haemorrhage; observed during the first hours from onset, and determines the poor prognosis. Intracerebral
Guidelines; haemorrhage, therefore, is a neurological emergency which must be diagnosed and treated
Stroke properly as soon as possible. In this guide we review the diagnostic procedures and factors that
influence the prognosis of patients with intracerebral haemorrhage and we establish recom-
mendations for the therapeutic strategy, systematic diagnosis, acute treatment and secondary
prevention for this condition.
© 2011 Sociedad Española de Neurología. Published by Elsevier España, S.L. All rights reserved.

PALABRAS CLAVE Guías de actuación clínica en la hemorragia intracerebral

Hemorragia
intracerebral; Resumen La hemorragia intracerebral sólo representa entre el 10 y el 15% de todos los ictus,
Guías; sin embargo condiciona un peor pronóstico, con unas tasas más elevadas de morbilidad y mor-
Ictus talidad. Es frecuente que durante las primeras horas tras el inicio de los síntomas se produzca
un empeoramiento clínico, lo cual condiciona un peor pronóstico, por lo que la hemorragia
intracerebral constituye una emergencia neurológica en la que debe realizarse un diagnós-
tico y tratamiento adecuado de manera precoz. En esta guía realizamos una revisión de los
procedimientos diagnósticos y los factores que influyen en el pronóstico de los pacientes con
hemorragia intracerebral y establecemos unas recomendaciones para la estrategia asistencial,

夽 Please cite this article as: Rodríguez-Yáñez M, et al. Guías de actuación clínica en la hemorragia intracerebral. Neurología.

2013;28:236—49.
∗ Corresponding author.

E-mail address: [email protected] (J. Castillo).

♦ The affiliations of the authors and composition of the committee are listed in Addendum 1.

2173-5808/$ – see front matter © 2011 Sociedad Española de Neurología. Published by Elsevier España, S.L. All rights reserved.
Clinical practice guidelines in intracerebral haemorrhage 237

sistemática diagnóstica, tratamiento en fase aguda y prevención secundaria en la hemorragia

intracerebral.
© 2011 Sociedad Española de Neurología. Publicado por Elsevier España, S.L. Todos los derechos
reservados.

Introduction important cause of ICH is cerebral amyloid angiopathy,

which is the leading cause of lobar haemorrhage in elderly
Intracerebral haemorrhage (ICH) refers to the collection of subjects. This degenerative process affects small arteries
blood within the cerebral parenchyma as the result of vas- and arterioles located in the leptomeninges and cerebral
cular rupture unrelated to trauma. Although the bleed may cortex. Haemorrhages of this type are superficial, often
leak into the ventricular system or the subarachnoid space, recurring and multiple, and tend to be located in poste-
it always begins in brain tissue. This trait distinguishes ICH rior areas of the brain. They appear in elderly subjects, and
from subarachnoid haemorrhage and primary intraventricu- up to half of all patients present cognitive decline.7 Lastly,
lar haemorrhage. there are other less common causes of ICH which are listed
Haemorrhages are categorised as primary or secondary in Table 1.
depending on the cause of the bleed. Primary ICHs are
the most common and they are caused by the rupture of
any blood vessel within the brain’s normal vascular sys- Care strategy and systematic diagnosis
tem after the vascular wall is weakened by degenerative
processes secondary to arterial hypertension (AHT) or amy- ICH is a neurological emergency, and therefore rapid diagno-
loid angiopathy. Secondary ICHs are caused by the rupture sis and management are fundamental; as mentioned before,
of blood vessels that are congenitally abnormal or newly clinical exacerbation is common in the first few hours fol-
formed, or of vessels that contain vascular wall abnormali- lowing ICH. This factor is directly associated with a poorer
ties or weaknesses caused by coagulation disorders. They are functional prognosis. A number of observational studies
associated with such entities as tumours, arteriovenous mal- show that 1 in 3 patients with supratentorial haemorr-
formations (AVM), coagulation disorders, substance abuse, hage and most patients with a posterior fossa haemorrhage
or haemorrhages inside areas of ischaemia.1 present an altered level of consciousness.8 Owing to the high
ICH incidence varies by country, race, age, and sex, and it risk of early neurological impairment, which is associated
is closely related to AHT prevalence. In Europe, its incidence with poor long-term prognosis, care must be provided to
rate is approximately 15 cases per 100 000 inhabitants.2 ICH patients as quickly as possible.
While ICH is only present in 10% to 15% of all strokes, it is
associated with a poorer prognosis and higher morbidity and
Pre-hospital care
mortality rates. The mortality rate during the first month
after ICH is 40.4%.3 Most deaths occur in the first 2 days,
and only 20% of the total patients are independent 6 months The main objective of pre-hospital care is maintaining
after having had an ICH.4 Mortality at 30 days is related to correct cardiovascular and respiratory function and trans-
the size and location of the ICH. In patients with an ini- porting the patient to the nearest hospital with facilities for
tial haemorrhage volume greater than 60 cm3 , mortality for acute-phase stroke patients. Additional objectives include
deep haemorrhages is 93%, and for lobar haemorrhages, 72%. taking the patient’s medical history, especially events occur-
If initial volume is less than 30 cm3 , mortality rates are 39% ring at symptom onset and information about prior medical
for deep haemorrhages, 7% for lobar haemorrhages, and 57% conditions. It is important to alert the receiving hospital
for cerebellar haemorrhages.3 prior to the arrival of a patient with a possible stroke so
The incidence of ICH is on the rise despite improved con- that staff can prepare the equipment needed to assess the
trol over certain risk factors. This is related to the ageing of stroke. This cuts down on delays in completing neuroimaging
the population. However, the higher incidence rate among tests in the emergency department.9
the elderly may also contribute to the decrease in mortal-
ity recorded in recent years, because of more pronounced Care in the emergency department
cerebral atrophy.
The most important risk factor for developing ICH in Once the haemodynamic and cardiorespiratory functions
all age groups and both sexes is AHT, whether systolic have been stabilised, further objectives include confirming
or diastolic. AHT is present in 60% of all cases. Chronic the type of stroke to differentiate a haemorrhage from
AHT provokes degenerative changes in arteriole walls that ischaemia or other brain lesions; gathering information
favour vascular obstructions. This in turn causes the lacunar about ICH aetiology; preventing potential complications;
infarcts, leukoaraiosis, and vascular rupture that are respon- and starting appropriate treatment.
sible for the appearance of ICH.5 AHT may also be an acute The clinical course of ICH may not offer data distinguish-
cause of ICH by affecting small arterioles that are at risk due ing that entity from other types of stroke unless there are
to hypertrophy of their walls. This leads to haemorrhages pathognomonic clinical features pointing to a cerebral hae-
such as those caused by certain drugs or haemorrhages morrhage. However, certain signs and symptoms are more
occurring after endarterectomy or angioplasty.6 Another suggestive of ICH than of ischaemia. One symptom that
238 M. Rodríguez-Yáñez et al.

associated with increased risk of cerebral bleeding

Table 1 Causes of non-traumatic intracerebral
(including arteriovenous malformations and intracranial
haemorrhage.
aneurysms).
High blood pressure In addition to assessing neurological deficit in the ini-
Amyloid angiopathy tial examination, doctors must evaluate respiration and
Ethanol the haemodynamic state. To this end, an electrocardio-
Haematological Von Willebrand factor deficiency gram and chest radiography are needed. A detailed physical
diseases Haemophilia examination that includes a cardiovascular study and oph-
Afibrinogenemia thalmoscopy is often helpful for establishing an aetiological
Hyperfibrinolysis syndromes diagnosis. In cases in which the patient has remained bedrid-
Idiopathic thrombotic den during long periods of time, doctors should check
thrombocytopenic purpura for potential associated complications, including pressure
Disseminated intravascular ulcers, compartment syndromes, rhabdomyolysis, and trau-
coagulation matic lesions.
Coagulation disorders and
thrombocytopenia in liver disease Laboratory tests
Thrombocytopenia
Thrombocythemia
It is important to perform blood tests to gather results for
Multiple myeloma
complete blood count, electrolytes, urea, creatinine, liver
Anticoagulants and Vitamin K antagonists
function parameters, and glucose. High creatinine and glu-
fibrinolytic drugs Heparin
cose levels are associated with haemorrhage growth and a
Streptokinase
poor functional prognosis.11,12 Doctors should also complete
Urokinase
a coagulation study including activated partial thromboplas-
Tissue plasminogen activator
tin time (APTT) and INR. This is done because haemorrhages
Brain tumours Primary tumours
associated with anticoagulant treatment are accompanied
Metastasis
by increased risk of morbidity and mortality13,14 and require
Vascular Aneurysms
urgent treatment to reverse the coagulation disorder.
malformations Arteriovenous malformations
Younger patients should undergo urine screening to
Venous angiomas
detect toxic substances such as cocaine and other sympath-
Cavernomas
omimetic drugs and women of childbearing age will require
Telangiectasias
a pregnancy test.
Moyamoya syndrome
Non-infectious Vasculitis
inflammatory Neuroimaging
vascular disease
Infectious Mycotic aneurysms The presence of sudden-onset focal neurological deficit sug-
inflammatory gests a vascular origin unless there is another proven cause.
vascular disease Although some of the symptoms described above, such as
sympathomimetic Cocaine headache, vomiting, and decreased level of consciousness,
drugs Amphetamines are suggestive of ICH, these findings are not specific and
Crack they do not enable us to differentiate between neurolog-
Nasal decongestants ical deficit caused by cerebral ischaemia and that caused
by a haemorrhage. For this reason, neuroimaging studies
are fundamental. Both computed tomography (CT) and mag-
appears frequently is headache, which is present in 40% of netic resonance imaging (MRI) may be used for the initial
ICH cases and only 17% of ischaemic stroke cases. Other com- diagnosis. CT is highly sensitive for identifying haemorrhage
mon symptoms, present in 50% of ICH cases, include nausea, during the acute phase, and it is regarded as the technique
vomiting, and decreased level of consciousness; these signs of choice. Gradient echo MRI sequences are as sensitive as
are exceptional in ischaemic stroke. We also find increased CT for detecting blood during the acute phase of stroke,
arterial blood pressure in almost 90% of ICH cases.10 and they are even more sensitive than CT for detecting old
When taking medical histories, doctors must emphasise haemorrhages.15 However, the availability, lower costs, and
data such as time of symptom onset, vascular risk factors shorter times associated with CT mean that this technique
(AHT, diabetes, hypercholesterolaemia), substance abuse is more commonly used than MRI.
(tobacco, alcohol, cocaine, amphetamines), drugs (antico- CT allows us to pinpoint the location of the haemorrhage
agulants, antiplatelet drugs, nasal decongestants, diet pills, and identify its effects (mass effect, oedema, ventricular
stimulants, sympathomimetic drugs), prior traumatic event extension, and subarachnoid extension). Furthermore,
or recent surgery (especially endarterectomy or carotid administering contrast intravenously lets us diagnose
angioplasty, which may be associated with reperfusion syn- certain secondary causes of ICH, such as AVMs or tumours.
drome), pre-existing cognitive decline (related to amyloid In the first hours of the process, ICH presents as increased
angiopathy), seizures, systemic illnesses related to coag- density in the cerebral parenchyma, which is explained by
ulation disorders (liver disease, vasculitis, cancer, blood the haemoglobin in the escaped blood. As the days pass,
dyscrasia), and any family history of neurological diseases the haemorrhage can be found in the centre of a hypodense
Clinical practice guidelines in intracerebral haemorrhage 239

ring. At first, this appearance is caused by retraction of the Conventional arteriography may be useful when there is
clot; at a later point, it is caused by vasogenic oedema. a strong suspicion of a secondary cause and results from
At the end of several weeks, the high initial density of the non-invasive studies are negative. Radiological signs that
haemorrhage begins to decrease from the perimeter toward suggest a secondary cause are presence of subarachnoid
the centre. The final stage of an ICH as viewed by CT is haemorrhage, unusual haemorrhage shape (non-circular),
total reabsorption of haemorrhagic tissue. This produces a oedema size not proportional to haemorrhage evolution
residual cavity that is indistinguishable from that left by an time, uncommon location, or presence of abnormal struc-
old cerebral infarct.16 tures. The probability of detecting a secondary cause by
Some data on the location and morphology of ICHs using angiography is higher in these cases.24 For suspected
detected using CT may be important to establish an aetio- vasculitis, conventional angiography is the technique of
logical diagnosis. The most common location of hypertensive choice. In some cases, as with cavernous angiomas, conven-
ICH is the putamen (30%—50%), followed by subcortical tional angiography may yield negative results. Arteriography
white matter (30%) and the cerebellum (16%). If the loca- is not useful, however, in hypertensive patients older than 45
tion is lobar, the role played by AHT is less significant and with haemorrhages in the putamen, thalamus, or posterior
amyloid angiopathy is more likely to be the cause. This fossa.25
is especially true in patients older than 60 years with a
certain level of cognitive decline.17 Other common causes
of lobar haemorrhages are arteriovenous malformations
(7%—14%), tumours (7%—9%), and blood dyscrasias, includ- Recommendations for the care strategy and system-
ing anticoagulant treatment (5%—20%). In 3% of all patients, atic diagnosis
the haemorrhage remains limited to the intraventricular
system.18 1. An emergency brain CT or MRI scan is recommended
Since the haemorrhage often grows during the acute on an emergency basis in order to distinguish
phase, and this phenomenon is associated with neurologi- between ICH and other ischaemic or structural
cal deterioration and increased morbidity and mortality,19 lesions (level of evidence 1, grade A recommenda-
research is being done on techniques that may help us pre- tion).
dict haemorrhage growth. The use of CT angiography with 2. CT angiography with contrast may be useful for
contrast may help identify patients at risk for haemorrhage identifying patients who are at risk for haemorrhage
expansion based on the presence of isolated contrast in the growth (level of evidence 2b, grade B recommenda-
haemorrhage (spot sign).20,21 This technique is also useful tion).
for detecting secondary causes of ICH, such as arteriovenous 3. CT angiography and/or MRI angiography may be
malformations, tumours, or venous thrombosis. useful for identifying structural lesions that are
MRI scans contribute further information about the stage aetiologically related to ICH when there is a suspi-
of development of the ICH. Differences in these scans have cion based on radiological findings (level of evidence
to do with the way that images of haemoglobin change 2a, grade B recommendation).
throughout the catabolism process. In the early stages of 4. Conventional angiography must be considered in
acute-phase ICH (initial hours), oxyhaemoglobin levels in the patients when the ICH aetiology has not been deter-
haemorrhage are high and the MRI shows hypointensities in mined by non-invasive methods and radiological
T1 and hyperintensities in T2. In later stages of acute-phase signs are suggestive of a structural lesion (level of
ICH (first few days), oxyhaemoglobin converts to deoxy- evidence 4, grade C recommendation).
haemoglobin from the centre of the bleed to its perimeter.
In the MR image, this appears as a hypointense area in
T2, surrounded by a hyperintense ring corresponding to the
oedema. In late stages of ICH (after several weeks), deoxy-
haemoglobin is transformed into methaemoglobin from the
perimeter to the centre. The change appears as a periph- Medical treatment
eral hyperintense signal in T1 which progressively extends
to the entire area of the haemorrhage. In the recovery Treatment for patients with ICH is fundamentally medical.
phase (months after onset), all of the haemoglobin has been It is based on maintaining vital functions, neurologi-
transformed into haemosiderin, which creates a pronounced cal monitoring, maintaining homeostasis, and preventing
hypointense signal in T2-weighted sequences. MRI gradient- complications.26 The key objective of all of these activities
echo sequences are highly sensitive for detecting small is to prevent increases in haemorrhage size, which would
chronic haemorrhages, called microbleeds, which measure provoke a mass effect, increase intracranial pressure, and
less than 5 mm. Microbleeds appear as hypointense pinpoint cause secondary neurological impairment. All ICH patients
lesions and indicate the presence of chronic haemosiderin must be cared for in hospitals that include a neurologist,
deposition.22 Magnetic resonance angiography (MRA) is a neurosurgeon, CT, stroke unit, and intensive care units that
useful technique for detecting vascular lesions associated are available 24 hours a day. If the patient does not require
with ICH. It has a high sensitivity for detecting aneurysms mechanical ventilation, care measures should be carried out
and AVMs.23 MRA is also useful during the venous phase when in the stroke unit,27—30 provided that the patient can be
there is a suspicion of sinus thrombosis as the cause of the examined by a neurosurgeon and has the option of being
haemorrhage. The technique is as reliable as CT angiography transferred to the intensive care unit at any time of day
with contrast during the venous phase. should it become necessary.
240 M. Rodríguez-Yáñez et al.

General care increases in arterial pressure include activation of the

neuroendocrine system (sympathetic, renin-angiotensin, or
Resuscitation glucocorticoid systems) due to stress and the elevation of
All patients with ICH must be cared for in hospitals with intracranial pressure (Cushing effect).
stroke units and ICUs available 24 hours a day. If the patient High arterial pressure values in patients with ICH may
does not require mechanical ventilation, life support be associated with increased haemorrhage growth,38 which
measures should be applied in the stroke unit, provided is another sign of poor patient prognosis. Arterial pressure
that the patient can be examined by a neurosurgeon and readings in cases of ischaemic stroke follow a U-shaped
has the option of being transferred to the intensive care curve, and both high and low values increase the risk
unit at any time of day if necessary. Admission to a general of neurological damage, mortality, and poor functional
ICU rather than a specialised neurological ICU increases prognosis.39 Animal models of ICH have described secondary
risk of death by a factor of 3.4.31 Likewise, admission to damage, possibly caused by mechanical compression of
a stroke unit increases probability of survival and a good microvessels, which induces an ischaemic area around the
functional prognosis by 64%.32 Recent population-based haemorrhage.40 This leads us to think that decreased arterial
studies suggest that good medical care has a significant pressure could contribute to reduced blood flow in the peri-
impact on mortality and morbidity in ICH.33 haemorrhagic region, thereby producing more pronounced
An initial assessment of the patient will allow us to neurological impairment. Based on these data, we recom-
evaluate the patient’s level of consciousness and ability to mend maintaining systolic blood pressure below 180 mm Hg
maintain spontaneous breathing. However, even in patients during the acute phase of ICH. However, neuroimaging stud-
with a high level of consciousness, it is recommended that ies have been unable to identify ischaemia around the
doctors know the oxygen saturation level. The simplest haemorrhage site in human clinical data,41,42 and this aspect
means of measuring oxygen saturation is by using a pulse remains controversial.
oximeter. If arterial oxygen saturation is less than 92%, the The INTERACT study43 provides new data regarding blood
patient will require an oxygen mask with a flow that will pressure management during the acute phase of ICH. This
raise oxygen saturation to above that threshold. Performing study was designed in order to evaluate how stricter control
an arterial blood gasometry study is optional and depends over arterial pressure would affect haemorrhage growth
on the patient’s condition. Up to a third of the patients with and the development of peri-lesional oedema. To that end,
supratentorial haemorrhage and almost all patients with the study included 404 patients with spontaneous ICHs that
a posterior fossa haemorrhage present decreased level of had appeared in the preceding 6 hours. Their systolic blood
consciousness or bulbar muscle dysfunction that results in pressure values were ≥150 mm Hg and ≤220 mm Hg. Patients
the need for intubation.34 Early intubation in patients who were randomly assigned to receive blood pressure treatment
have suffered from very large haemorrhages accompanied either according to recommendations in international guide-
by decreased level of consciousness may help prevent lines or according to stricter standards. In patients whose
aspiration pneumonia. In general, endotracheal intubation blood pressure was controlled according to international
and gastric aspiration are indicated in patients with a score guidelines, systolic pressure was kept below 180 mm Hg. The
of less than 8 on the Glasgow coma scale (GCS). Intubation objective in the group of patients under stricter standards
should be performed after administration of drugs that was to reach a systolic blood pressure of 140 mm Hg during
suppress the tracheal reflex, since that reflex may cause the first hour and maintain levels below that threshold dur-
increased intracranial pressure and exacerbate the neuro- ing the following 7 days. Results from the study show that
logical lesion. In any case, the indication for orotracheal patients assigned to the group with stricter blood pressure
intubation is debatable. There may be reason to consider control presented less haemorrhage growth and a tendency
it only if doctors plan to apply other treatment measures in for the peri-haemorrhagic oedema to decrease. There were
order to improve the patient’s neurological situation. no signs of increased neurological decline or poorer func-
tional prognosis, but the study was not designed to evaluate
these parameters. Data from the study seem to indicate
Neurological monitoring
that strict control over blood pressure is safe. However,
Since a high number of patients experience a decline in the
we have yet to determine the most appropriate level of
hours following the stroke, periodic monitoring of the level
arterial pressure, the correct duration for antihypertensive
of consciousness and the neurological deficit should be per-
treatment, and the effect of these parameters on the
formed during at least the first 72 hours. The most widely
functional prognosis of ICH patients. The study INTERACT 2
recommended scales are the NIH stroke scale (NIHSS) for
is currently underway44 and its main objective is to evaluate
measuring neurological deficit35 and the GCS for measuring
how maintaining strict control over blood pressure during
level of consciousness due to its simplicity and reliability.36
the acute phase affects functional prognosis in ICH patients.
The drugs recommended for blood pressure control are
Control over arterial pressure those that do not induce cerebral vasodilation or sudden
In most patients with an intracerebral haemorrhage, hypotension, such as intravenous labetalol (loading doses
arterial pressure readings are elevated during the acute of 10 to 20 mg in 1 to 2 minutes, repeated every 1 to
phase. In fact, values are often higher than those observed 20 minutes until the blood pressure reaches the desired level
in cases of ischaemic stroke.37 Although blood pressure or the maximum dose of 200 mg has been given); intravenous
generally decreases spontaneously in the days following enalapril (1 mg bolus); or intravenous urapidil (25 mg bolus
the haemorrhage, high readings persist in many patients. in 20 s, repeating procedure after 5 minutes in absence of a
Potential pathophysiological mechanisms that promote response).
Clinical practice guidelines in intracerebral haemorrhage 241

Glycaemic control should be administered to patients with both ICH and

High glycaemic levels upon admission are associated with haemophilia.
increased risk of mortality and poor prognosis in patients Recombinant activated factor VII has also been investi-
with intracerebral haemorrhage.45,46 One clinical trial in gated in ICH patients without disorders of haemostasis. A
critical care patients with or without acute stroke shows that phase 2 study has shown that recombinant activated factor
maintaining glucose levels between 80 and 110 mg/dL using VII limits haemorrhage growth and improves patients’ func-
intravenous insulin has been associated with higher inci- tional prognosis compared to a placebo, despite increasing
dence rates of hypoglycaemia episodes, whether systemic the frequency of thromboembolic complications.55 A phase
or cerebral. It may also be linked to an even higher risk of 3 study confirmed that delivering recombinant activated
mortality among the patients receiving this treatment.47,48 factor VII limits haemorrhage growth, but no significant
There are no intervention studies designed specifically differences in prognosis could be found with respect to a
for ICH, and as a result, the target level for glycaemic con- placebo.56 It has not yet been shown whether recombinant
trol in ICH patients is not completely clear. However, glucose activated factor VII can deliver benefits in selected patients,
levels above 155 mg/dL in ischaemic stroke have been asso- but in any case, administering this treatment to all ICH
ciated with poor prognosis,49 and it is therefore appropriate patients indiscriminately does not improve their prognosis
to correct levels above this threshold. Hypoglycaemia must and furthermore, it increases the risk of thromboembolic
be prevented by administering a 10% to 20% dextrose solu- complications.
tion. Patients with ICH and thrombocytopenia must receive
transfusions of platelet concentrate. Data from patients
without thrombocytopenia who are being treated with
Temperature control
antiplatelet drugs are contradictory. Platelet dysfunction
Fever owing to any cause is associated with neurological
has been linked to increased haemorrhage volume and a
impairment and poor prognosis.50 Although there is no
poor functional result57 ; however, one clinical trial inves-
evidence that treatment decreases this risk, symptomatic
tigating neuroprotection in cerebral haemorrhages58 found
treatment with antipyretic drugs such as paracetamol is rec-
no differences between patients receiving a placebo and
ommended. For patients with fever, we recommend ordering
those previously treated with antiplatelet drugs. Therefore,
a chest radiography, cultures of blood, sputum, and urine,
platelet replacement therapy is not indicated for patients
and urine sediment analysis in order to identify and treat
taking antiplatelet drugs and those whose platelet count is
associated infectious processes. Peripheral blood vessels
normal.
should be systematically checked to rule out phlebitis.
Some recent studies have demonstrated benefits of mod-
erate hypothermia in certain conditions including head Preventing complications
trauma. However, its effects have not been explored in cases
of patients with ICH. Deep vein thrombosis and pulmonary embolism
Patients with ICH are at an increased risk of suffering throm-
Mana ging haemostasis boembolic complications.59 Sporadic use of compression
Haemostatic alterations, such as treatment with oral anti- stockings has not been shown to be effective for preventing
coagulants, coagulation factor deficiencies, or platelet deep vein thrombosis.60 However, the combination of inter-
abnormalities, can contribute to haemorrhage growth, mittent mechanical compression and compression stockings
which in turn leads to neurological impairment. It is there- is much more effective.61 The use of low molecular weight
fore important to correct these factors as quickly as heparin beginning on day 1 after a cerebral haemorrhage
possible. decreases the risk of thromboembolic complications in ICH
In cases in which the patient is being treated with oral patients and does not increase the risk of bleeding.62
anticoagulants, the INR must be corrected to reach nor-
mal values as soon as possible.51 This should be done using Seizures
intravenous vitamin K and/or fresh frozen plasma and/or The presence of seizures increases the brain’s metabolic
prothrombin complex concentrate.52,53 The effectiveness of demand and exacerbates neurological damage in patients
fresh frozen plasma is limited by the risk of allergic reac- with ICH. If seizures appear, they should initially be treated
tions and infections, as well as by the considerations of with benzodiazepine, followed by antiepileptic drugs. How-
processing time and hypervolaemia. Prothrombin complex ever, administering antiepileptic drugs to ICH patients
concentrates also contain factors II, VII, IX, and X, and they who have not experienced a seizure is associated with
are able to normalise INR values quickly. On this basis, they increased morbidity and mortality, especially in the case
constitute the treatment of choice for cases of ICH related to of phenytoin.63,64 Prophylactic treatment for seizures is not
oral anticoagulants.54 However, they must be combined with recommended.
vitamin K, since the half-life of oral anticoagulants is much
longer than those of vitamin K-dependent clotting factors.
In cases in which patients have received intravenous hep- Managing intracranial pressure
arin and display prolonged APTT, doctors should administer Control over intracranial pressure (ICP) is one of the specific
protamine sulphate. If ICH has occurred due to fibrinolytic treatment objectives in ICH, and the approach should be
treatment, it may be necessary to administer fresh frozen directed at the underlying cause. The most common causes
plasma, platelets, or antifibrinolytics such as aminocaproic of high ICP are hydrocephalus due to intraventricular hae-
acid or tranexamic acid. Recombinant activated factor VII morrhage and the mass effect of the haemorrhage.
242 M. Rodríguez-Yáñez et al.

Placing devices that measure ICP increases the risk of ICH prognosis
haemorrhage and infection, and such devices should not Many different studies have turned up factors that may
be used as routine treatment. However, there are also be related to patient prognosis. These variables include
non-invasive techniques that allow us to estimate intracra- age, scores on the GCS and NIHSS scales, haemorrhage
nial pressure in patients with ICH, such as the transcranial volume and location, and the presence of intraventricular
Doppler test. An increase in the pulsatility index in the mid- haemorrhage.70 Data which may reflect a poor prognosis
dle cerebral artery of the unaffected hemisphere indicates may be interpreted as a reason for limiting care. This deci-
intracranial hypertension, and this has been shown to pre- sion affects mortality, and early mortality in particular.71—73
dict mortality.65 Current evidence suggests that establishing a sure prognosis
Data on managing ICP in ICH are limited; recom- is impossible. We therefore do not recommend deciding to
mendations have been extrapolated from those used in limit care in early stages.
the management of patients with head trauma.66 Doctors
recommend considering ICP treatment and management
in patients with ICH with a Glasgow scale score ≤8, Recommendations in medical treatment
clinical evidence of transtentorial herniation, significant
intraventricular haemorrhage, or hydrocephalus. Neverthe-
less, we must be aware that very few studies attempt General care
to show the utility of ICP monitoring in ICH patients.
Most such studies were unable to discriminate between Life support and oxygen saturation
patients who might be candidates for surgical evacuation 1. If arterial oxygen saturation is less than 92%, the
of the haemorrhage and candidates for medical treatment patient will require an oxygen mask with a flow
only. sufficient to maintain oxygen saturation above that
Centring the head and raising the headboard to an angle threshold.
of 20◦ to 30◦ improves venous return and may decrease 2. Early intubation is recommended in patients with a
PIC slightly. Hyperventilation decreases partial pressure of massive ICH and low level of consciousness (GCS < 8)
oxygen in arterial blood, which leads to cerebral vaso- if the patient’s prior functional state is good, but
constriction and a lowered ICP. The target is to reach not if all brainstem signs have disappeared (level of
partial pressure of CO2 between 28 and 35 mm Hg and evidence 5, grade C recommendation).
subsequently maintain pressure between 25 and 30 mm Hg
if the ICP remains high. This results in rapid decrease Neurological monitoring
of ICP, although the effect is temporary and other mea- 1. Level of consciousness and neurological deficit must
sures will have to be taken in order for ICP to remain be evaluated periodically during at least the first
under control. Conditions that can cause increased ICP 72 hours after the stroke. Neurological impairment
must be avoided, including fever, Valsalva-like manoeu- should be measured using the NIHSS scale; level of
vres (coughing or vomiting), seizures, stress, pain, AHT, consciousness is monitored using the Glasgow coma
and hyponatraemia. Osmotherapy reduces ICP by increasing scale (level of evidence 5, grade C recommenda-
osmolarity in plasma, which in turn displaces water from tion).
healthy brain tissue into the vascular compartment. The
most commonly employed drugs of this type are mannitol
Arterial pressure
and loop diuretics such as furosemide. Recommendations
1. The current recommendation, as we await results
for dosing 20% mannitol range from 0.7 to 1 g/kg (250 mL)
from new clinical trials, is to treat patients whose
followed by 0.3 to 0.5 g/kg (125 mL) every 3 to 8 hours.
systolic blood pressure exceeds 180 mm Hg (level of
Treatment should not be extended beyond 5 days so as
evidence 2b, grade C recommendation).
to avoid the rebound effect. Furosemide (10 mg every
2. Rapid reduction of systolic blood pressure to the
2—8 hours) may be used simultaneously to maintain the
limit of 140 mm Hg is safe in patients whose sys-
osmotic gradient. Using corticosteroids for this purpose
tolic blood pressure readings fall between 150 and
is not effective and may even increase the number of
220 mm Hg (level of evidence 2a, grade B recom-
complications.67 Sedation with intravenous drugs, such as
mendation).
benzodiazepines, barbiturates, narcotics, and butyrophe-
nones, reduces brain metabolism and decreases cerebral
blood flow and ICP. In contrast, sedation also gives rise to Glycaemia
numerous complications which include arterial hypotension 1. Blood glucose levels must be checked regularly and
and respiratory infections. hyperglycaemia above 155 mg/dL is to be avoided
Hydrocephalus caused by the presence of an intraven- (level of evidence 2c, grade C recommendation).
tricular bleed is one of the factors associated with a If the glucose level exceeds that threshold, it
poor prognosis and increased mortality.68,69 Ventriculostomy should be corrected with insulin. Glucose levels
must be considered in cases in which hydrocephalus and below 70 mg/dL must be corrected with 10% to 20%
a decreased level of consciousness are both present. A dextrose (level of evidence 5, grade C recommen-
randomised study named CLEAR III, currently underway, is dation).
evaluating the efficacy and safety of intraventricular infu-
sion of thrombolytic drugs in patients with intraparenchymal
haemorrhage and ventricular invasion.
Clinical practice guidelines in intracerebral haemorrhage 243

Temperature 3. Although osmotic diuretics are recommended as the

1. Doctors recommend treating hyperthermia above first treatment option, they are not indicated for
37.5 ◦ C with intravenous paracetamol (level of evi- prophylactic use (level of evidence 5, grade C rec-
dence 5, grade C recommendation). ommendation).
Managing haemostasis 4. Doctors recommend hyperventilation in cases that
do not respond to treatment with osmotic diuret-
ics, provided that the patient has a good functional
1. Patients with coagulation factor deficiency or prognosis (level of evidence 5, grade C recommen-
severe thrombocytopenia should be treated with dation).
the lacking coagulation factors or platelets, 5. Corticosteroids are not recommended as treatment
respectively (level of evidence 1, grade B recom- for primary ICH (level of evidence 2, grade B rec-
mendation). ommendation).
2. Patients on anticoagulant treatment with ICH and
elevated INR should receive intravenous prothrom-
bin complex concentrate and vitamin K, plus fresh
plasma if necessary, to replace vitamin K-dependent Surgical treatment
factors until INR level is normalised (level of evi-
dence 1, grade B recommendation). The question of whether or not an ICH patient should be
3. Patients who have undergone intravenous hep- treated surgically is controversial. While surgery may reduce
arin treatment and have a prolonged APTT should the effects stemming from the mechanical compression
receive treatment with protamine sulphate (level exerted by the haemorrhage and also decrease the toxic
of evidence 5, grade C recommendation). effect of blood on nearby brain tissue, surgical risks may
4. Patients with ICH who have undergone thrombolytic be high. In most patients, the benefits of surgery do not
treatment should receive a transfusion of fresh outweigh the procedure’s potential for harm.
plasma and platelets or antifibrinolytic drugs such One important factor in the decision of whether to treat
as aminocaproic acid or tranexamic acid (level of ICH surgically is the haemorrhage location. Cerebellar haem-
evidence 5, grade C recommendation). orrhages larger than 3 cm in diameter, those compressing the
brainstem, or those with hydrocephalus respond better to
Preventing complications surgical treatment than to medical treatment.74,75 In these
cases, placing a ventricular shunt without evacuating the
Deep vein thrombosis and pulmonary embolism haemorrhage is insufficient, and shunt placement with no
additional actions is not recommended. In contrast, surgery
is not indicated for cerebellar haemorrhages that measure
1. A combination of intermittent mechanical compres-
less than 3 cm and do not compress the brainstem or involve
sion and compression stockings should be used to
hydrocephalus.
prevent deep vein thrombosis (level of evidence 1,
The clinical trial STICH observed that patients with a
recommendation level B). Beginning on day 1, it is
lobar haemorrhage located less than 1 cm from the cere-
possible to administer prophylactic treatment with
bral cortex tended to benefit from surgical treatment, but
low molecular weight heparin (level of evidence 2b,
the tendency was not statistically significant.76 They also
grade B recommendation).
discovered a non-statistically significant tendency toward
benefiting from surgery in patients with lobar haemorrhage
Seizures and GCS scores between 9 and 12. However, further clinical
trials will be needed to demonstrate this benefit. In cases
1. If seizures appear, the patient will require of haemorrhages located more than 1 cm from the cerebral
antiepileptic drugs (level of evidence 1, grade A cortex and a GCS score ≤8, prognosis is poorer in patients
recommendation). who undergo surgical treatment.77
2. Prophylactic treatment with antiepileptic drugs is Related studies on haemorrhages located in basal gan-
not indicated (level of evidence 3, grade B recom- glia do not show better results with surgical treatment. We
mendation). must also be mindful of the fact that gaining access to the
haemorrhage will involve passing through healthy brain tis-
Managing intracranial pressure
sue, meaning that the procedure will produce more severe
sequelae.77,78
1. ICP must be monitored in patients with a Recommended surgical treatment techniques include
GCS ≤ 8 and signs of transtentorial herniation or performing a craniectomy with decompression and evacu-
hydrocephalus (level of evidence 2b, grade C rec- ation of the haemorrhage, but attempts have been made
ommendation). at developing less invasive techniques. Certain projects
2. Placing a ventricular shunt should be considered for have studied the benefits of stereotactic surgery combined
patients with hydrocephalus (level of evidence 2a, with local thrombolysis78,80 or endoscopic aspiration.81,82
grade B recommendation). These techniques eliminate the haemorrhage more fully
and decrease mortality when they are performed in the
first 72 hours. Nevertheless, they have not been shown to
244 M. Rodríguez-Yáñez et al.

improve patients’ functional prognosis. One clinical trial during the acute phase except in patients at high risk
compared surgery using minimally invasive craniopuncture for thromboembolic events (for example, those fitted with
with medical treatment in cases of small-volume haemor- mechanical valves) and at low risk for a haemorrhage.90
rhages in the basal ganglia. The report observes that the When thromboembolic risk is high (CHA2 DS2 -VASc score ≥2),
technique is safe and may improve functional prognosis in doctors recommend recommencing oral anticoagulants 7 to
patients with this type of haemorrhage.79 10 days after the stroke.91 Antiplatelet drugs have a less pro-
The optimal moment in which to surgically evacuate the nounced effect on haemorrhage risk and severity than oral
haemorrhage is also a matter of debate. Studies of surgical anticoagulants do.92 They may therefore constitute a treat-
procedures performed within 24, 48, 72, or 96 hours of the ment alternative in patients who have a moderate level of
haemorrhage have found no differences in outcome except risk (CHA2 DS2 -VASc ≤1) or who are functionally dependent
with regard to patients treated with minimally invasive tech- (modified Rankin scale 4—5).91
niques, as indicated above. In haemorrhages secondary to an underlying lesion, spe-
cific treatment decreases risk of recurrence. For example,
surgery may be recommended for cavernous angiomas that
Recommendations for surgical treatment are surgically accessible and have a bleed rate of 0.7% per
year per lesion,93 depending on the risk of a new haemorr-
hage. A better approach for deep lesions is close monitoring;
1. Surgical treatment is recommended as soon as pos- surgery should be reserved for cases in which impairment is
sible for patients with cerebellar haemorrhages who progressive or bleeding is recurrent. Risk of rebleeding in
present with neurological impairment, brainstem AVMs is high at 18% the first year94 and 2% per year in later
compression, or hydrocephalus (level of evidence years.95 Treatment that excludes the AVM from the circula-
1, grade B recommendation). tory system is recommended where possible. In this case,
2. In patients with neurological impairment and a alternatives include surgical treatment, endovascular ther-
lobar haemorrhage exceeding 30 mL in volume and apy, and radiosurgery. Surgical treatment of ICH depends
located less than 1 cm from the cerebral cortex, sur- on the location. Haemorrhages located in the basal gan-
gical treatment should also be considered (level of glia, diencephalon, or brainstem are typically inoperable.
evidence 2b, grade B recommendation). Endovascular treatment was initially developed to facili-
3. Evacuation procedures are not recommended for tate resection of very large AVMs, or as an alternative to
deep haemorrhages (level of evidence 2, grade high-risk surgery.96 However, when lesions are small, com-
B recommendation). Although minimally invasive plete occlusion may be achieved with endovascular therapy.
surgery may be an alternative in the future, data are Radiosurgery is more effective in small AVMs (<3 cm)97 and
not sufficient to recommend stereotactic surgery to may also be used for AVMs that cannot be reached with
evacuate haemorrhages at the present time (level any other technique. In ICH secondary to neoplasia, surgical
of evidence 2, grade B recommendation). treatment is generally used to excise the underlying tumour.
Nevertheless, treatment depends on the patient’s functional
condition and the tumour type and location.

Secondary prevention

The risk of recurrence after a first ICH is between 2.1% and Recommendations for secondary prevention
3.7% yearly.83,84 In addition, lobar haemorrhages related to
amyloid angiopathy,85 haemorrhages secondary to anticoag- 1. Maintaining blood pressure values below
ulant treatment,84 history of prior cerebral haemorrhage,86 120/80 mm Hg is recommended for all patients
advanced age,84 and microbleeds detected by gradient echo with ICH (level of evidence 2a, grade B recommen-
MRI87 increase the risk of recurrence. dation).
AHT is the modifiable factor with the most influence 2. Anticoagulants should not be administered fol-
on risk of ICH recurrence, which is why proper blood lowing a lobar ICH in cases with non-valvular
pressure control is so important. Good control over blood atrial fibrillation (level of evidence 2a, grade
pressure lowers risk of ICH recurrence, whether for hyper- B recommendation). Antiplatelet drugs may be
tensive haemorrhages or for bleeds secondary to amyloid administered to these patients as an alternative to
angiopathy.88 Although the optimal blood pressure value for anticoagulants (level of evidence 2, grade B recom-
reducing risk of ICH recurrence is unknown, maintaining nor- mendation).
mal blood pressure values (below 120/80 mm Hg) seems to 3. In cases of accessible cavernous angiomas, doc-
be a reasonable choice.89 tors should evaluate surgical treatment according
Oral anticoagulants increase risk of ICH recurrence,84 and to the risk of bleeding (level of evidence 5, grade
the benefits of anticoagulation to prevent thromboembolic D recommendation). Monitoring is recommended
events must therefore be weighed against the risk of future for haemorrhages at deep locations; surgery should
ICHs. Risk of recurrence is higher in lobar haemorrhages, be considered in cases of rebleeding or increasing
which is why anticoagulant treatment should be suspended neurological deficit (level of evidence 5, grade D
definitively in patients with atrial fibrillation.90 In cases of recommendation).
deep haemorrhages, risk of recurrence is lower. Generally
speaking, doctors should consider suspending anticoagulants
Clinical practice guidelines in intracerebral haemorrhage 245

Madrid; Pablo Irimia, Clínica Universitaria de Navarra, Pam-

4. Recommended treatments for AVMs may be surgi- plona; Aida Lago, Hospital Universitario La Fe, Valencia;
cal, endovascular, and/or radiosurgical depending José Maestre, Hospital Universitario Virgen de las Nieves,
on the surgical risk and the size and location of the Granada; Jaime Masjuan, Hospital Universitario Ramón y
lesion (level of evidence 5, grade D recommenda- Cajal, Madrid; Joan Martí-Fábregas, Hospital de la Santa
tion). Creu i Sant Pau, Barcelona; Patricia Martínez-Sánchez,
Hospital Universitario La Paz, Madrid; Eduardo Martínez-
Vila, Clínica Universitaria de Navarra, Pamplona; Carlos
These clinical guidelines are rewritten periodically Molina, Hospital Universitario Vall d’Hebron, Barcelona;
because they must reflect a continuous series of advances Ana Morales, Hospital Universitario Virgen de la Arrix-
in clinical trials. They therefore draw from previous SEN aca, Murcia; Florentino Nombela, Hospital Universitario La
recommendations, as well as from current recommenda- Princesa, Madrid; Francisco Purroy, Hospital Universitario
tions by the European Stroke Initiative98 and the American Arnau de Vilanova, Lérida; Marc Ribó, Hospital Universitari
Heart Association Stroke Council.99 These recommenda- Vall d’Hebron, Barcelona; Manuel Rodríguez-Yáñez, Hospi-
tions were taken into account in the process of elaborating tal Clínico Universitario, Santiago de Compostela; Jaime
the guidelines we present here. Likewise, in order to Roquer, Hospital del Mar, Barcelona; Francisco Rubio, Hos-
prepare guidelines according to the standard set by inter- pital Universitario de Bellvitge, Barcelona; Tomás Segura,
national publications, we used the levels of evidence Hospital Universitario de Albacete, Albacete; Joaquín Ser-
and grades of recommendation published by the Centre ena, Hospital Josep Trueta, Gerona; Patricia Simal, Hospital
for Evidence-Based Medicine at the University of Oxford Clínico Universitario San Carlos, Madrid; Javier Tejada, Hos-
(Addenda 2 and 3).100 pital Universitario de León, León; José Vivancos, Hospital
Universitario La Princesa, Madrid.

Conflict of interest A.2. Review or institutional committee

The authors have no conflicts of interest to declare. José Álvarez-Sabín, Hospital Universitari Vall d’Hebron,
Barcelona; José Castillo, Hospital Clínico Universitario,
Santiago de Compostela; Exuperio Díez-Tejedor, Hospital
Addendum 1. Ad hoc committee of the SEN Universitario La Paz, Madrid; Antonio Gil-Núñez, Hospital
Study Group for Cerebrovascular Diseases Universitario Gregorio Marañón, Madrid; José Larracoechea,
constituted to draw up clinical practice Hospital de Cruces, Bilbao; Eduardo Martínez-Vila, Clínica
Universitaria de Navarra, Pamplona; Jaime Masjuan, Hospi-
guidelines for stroke. tal Universitario Ramón y Cajal, Madrid; Jorge Matías-Guiu,
Hospital Clínico Universitario San Carlos, Madrid; Francisco
Coordinator: Exuperio Díez-Tejedor, Hospital Universitario Rubio, Hospital de Bellvitge, Barcelona.
La Paz, Madrid.

A.1. Drafting committee

Addendum 2. Classification of levels of
Exuperio Díez-Tejedor (Coord), Hospital Universitario La evidence
Paz, Madrid; Blanca Fuentes (Secretary), Hospital Uni-
versitario La Paz, Madrid; María Alonso de Leciñana, Level of evidence Type of study
Hospital Universitario Ramón y Cajal, Madrid; José Álvarez-
1a Systematic review of
Sabin, Hospital Universitari Vall d’Hebron, Barcelona; Juan
randomised clinical trials
Arenillas, Hospital Universitario Clínico de Valladolid; Ser-
(with homogeneity)
gio Calleja, Hospital Universitario Central de Asturias,
1b Randomised clinical trial
Oviedo; Ignacio Casado, Hospital San Pedro, Cáceres; Mar
with narrow confidence
Castellanos, Hospital Josep Trueta, Girona; José Castillo,
interval
Hospital Clínico Universitario, Santiago de Compostela;
1c Clinical practice (all or
Antonio Dávalos, Hospital Universitari Germans Trias i Pujol,
none)a
Badalona; Fernando Díaz-Otero, Hospital Universitario Gre-
2a Systematic review of cohort
gorio Marañón, Madrid; Exuperio Díez-Tejedor, Hospital
studies (with homogeneity)
Universitario La Paz, Madrid; José Antonio Egido, Hospital
2b Cohort study or low quality
Clínico Universitario San Carlos, Madrid; Juan Carlos Fer-
randomised clinical trialb
nández, Hospital Universitario Dr. Negrín, Las Palmas; Mar
2c ‘‘Outcomes’’ research,c
Freijo, Hospital Universitario de Basurto, Bilbao; Blanca
ecological studies
Fuentes, Hospital Universitario La Paz, Madrid; Jaime Gál-
3a Systematic reviews of
lego, Hospital General de Navarra, Pamplona; Andrés García
case—control studies (with
Pastor, Hospital Universitario Gregorio Marañón, Madrid;
homogeneity)
Antonio Gil-Núñez, Hospital Universitario Gregorio Marañón,
3b Case—control studies
Madrid; Francisco Gilo, Hospital Universitario La Princesa,
246 M. Rodríguez-Yáñez et al.

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