The term subarachnoid haemorrhage (SAH) refers to blood within the subarachnoid space. It can occur for a variety of reasons:
Cerebral aneurysm (most common)
Non-aneurysmal e.g. Arteriovenous malformation (AVM)
Much of the management noted here relates to SAH of an aneurysmal nature, and that of a traumatic nature is considered elsewhere.
The most common cause of non-traumatic SAH is from an aneurysm. This is a bulging of one of the cerebral arteries. It is most often a saccular (berry) aneurysm (in 85%). The rare causes include: AVMs, mycotic aneurysms, and those in people with bleeding disorders. The blood in the subarachnoid space cause irritation of the meninges, and this is responsible for some of the clinical features.
There is some genetic component and first degree family members have a 3 to 7 fold increased risk. Specific inheritable disorders are rare though. Risk factors include:
sympathomimetic drug use (e.g. cocaine).
The primary presentation of non-traumatic SAH involves a headache. This is a common presentation to the ED and SAH is probably the most serious cause, accounting for 1-3% of cases. There can also be a history of prodromal symptoms, which may represent effects of sentinel bleeds or mass effect from an aneurysm.
The ‘classic’ features of a SAH are:
Sudden onset - often described as ‘thunderclap’
Often described as ‘worst headache ever’
Symptoms of meningeal irritation
Collapse/Loss of consciousness
Other symptoms could include:
A number of patients may have no detectable abnormality on neurological examination, making it difficult to determine which patients with headache warrant further investigation. A large study by Perry and colleagues suggested that the presence of one of 6 high risk features could be used as a prompt for further investigation. They have named this the Ottawa SAH rule (here):
Neck pain or stiffness
Witnessed loss of consciousness
Onset during exertion
‘Thunderclap headache’ - instantly peaking pain
Limited neck flexion on examination
This is for adult patients with non-traumatic headache with maximum intensity in under 1 hour, excluding those with abnormal neurology, previous SAH, brain tumours or known chronic headache.
The most common age is between 40 and 65 years old, but it can occur at any age.
Clinical findings may be completely normal. A common finding is a mild to moderate elevation of BP (in around 50%). This may become labile if ICP increases. The SAH may trigger a tachycardia which may persist for several days. Similarly, meningeal irritation may lead to a pyrexia (common after the fourth day post bleed).
Neurological abnormalities are found in around 25% of patients. An altered conscious level can often be noted. Focal neurology may include cranial nerves or pyramidal symptoms. Seizures may also occur.
Cranial nerve abnormalities reportedly occur in 25%. An oculomotor nerve palsy is the most common, arising from a ruptured posterior communicating artery aneurysm. Hemiparesis may result from a middle cerebral artery aneurysm (the most common culprit for motor deficits). Leg monoparesis may result from an anterior communicating artery aneurysm. An abducens nerve palsy is more commonly from raised ICP than from a local cause.
Non-contrast CT scan of the head is generally the first imaging choice. This can detect SAH with a high degree of sensitivity and specificity, particularly when done early and with 3rd generation CT scanners. This is because of the diffusion away and breakdown of the fresh blood over time, making it less visible radiographically. A large Canadian study (Perry et al) described a negative predictive value of 99.4% (99.1-99.6%) and positive predictive value of 100 (98.3-100%) if taken within 6 hours of symptom onset. A negative CT scan taken within 6 hours of headache onset can probably therefore fairly confidently exclude a SAH as the cause (dependent of CT scanner and experience of radiologist). Previous quotes about the sensitivity of CT scans are lower than this.
When SAH is confirmed, angiography of the cerebral vessels is performed to try and identify a culprit aneurysm.
If there is doubt about the diagnosis of SAH, a lumbar puncture has traditionally been the investigation of choice. As well as providing information about alternative diagnoses for the headache (e.g. meningitis) there is specific testing of the CSF for red blood cells and xanthochromia. RBCs can be seen in the CSF following the SAH, but they also may be introduced there by the trauma of the lumbar puncture itself. Serial, numbered samples of CSF are taken, and the number of RBCs in the final tube is used as an estimate of the ‘true’ RBC content of the CSF.
After about 6 hours following a SAH, the RBCs in the CSF begin to lyse, and produce breakdown products. This results in a yellow discoloration of the CSF, termed xanthochromia (greek Xanthos = yellow) that can be detected in the laboratory. The presence of cell breakdown products proves that blood was in the CSF before the lumbar puncture.
These should include other routine tests, depending on the specific clinical picture, usually including a full blood panel. ECG recording may demonstrate notable ECG changes as a result of the SAH, include ST elevation, mimicking an STEMI.
There are a number of systems for rating the severity of the SAH.
The WFNS (World Federation of Neurological Surgeons) grading is a common scale for classifying the severity of the SAH, based primarily on the patient’s GCS:
GCS 15 with no motor deficit
GCS 13-14 with no motor deficit
GCS 13-14 with motor deficit
GCS 7-12 with or without motor deficit
GCS 3-6 with or without motor deficit
This system is useful as it was constructed to highlight some of the key prognostic features in patients with SAH. The depression of conscious level is recognised as having the biggest impact on mortality, whilst the presence of motor deficit is recognised as having the biggest impact on disability. There is some debate as to the exact role, but a worse grade is generally associated with a worse prognosis.
The Hunt & Hess scale has also been used previously, but suffers from some degree of subjectivity, especially given the nature of the terms relating to conscious level. This was also derived from the patient’s neurology from a collection of conscious level, degree of meningeal irritation, and severity of neurological deficit.
Asymptomatic or mild headache, slight nuchal rigidity
Moderate to severe headache, nuchal rigidity, cranial nerve deficit but no other neurological deficit
Drowsiness/confusion, mild focal neurology
Stupor, moderate/severe hemiparesis
Coma, decerebrate posturing
There is also radiological grading of SAH severity, such as the Fisher scale:
No haemorrhage evident
SAH < 1mm thick
SAH > 1mm thick
SAH (any thickness) with intraventricular or intraparenchymal extension
It is to be noted that the values used are based on pretty old CT scanners, and as such on current scans grades 1 and 2 are uncommon.
Some grading systems exist which combine clinical and radiological findings, such as the Ogilvy and Carter system. When thinking of grading, it’s important to remember that some factors may falsely affect the grade of the patient e.g. physiological disturbance, post-ictal.
Initial management, as with all acutely unwell patients, involves an ABCDE approach. Any life threatening issues must but dealt with as they are encountered and the initial resuscitation of the obtunded patient is important to minimise secondary injury. This must be done as a priority, even though there may be a need to quickly transfer for neurosurgical intervention. The AAGBI guidance on this is useful (See link below).
Further management also focuses on preventing complications from developing. One arm of this is surgical, another is medical.
Initial surgical management is primarily to secure the aneurysm to prevent further bleeds from happening. This can be achieved by either coiling or clipping it.
This is an endovascular approach where platinum microcoils are passed into the lumen of the aneurysm and obliterate it. The approach is usually via a catheter in the femoral artery. The International Subarachnoid Aneurysm Trial (ISAT) in 2002 compared coiling with clipping in 2143 patients and demonstrated an improvement in independent survival when coiling was employed. This benefit persisted for at least 7 years, although the risk of late rebleeding was higher. As such, coiling is generally the prefered surgical intervention. Not all aneurysm are amenable to this approach, and in these cases, clipping of the aneurysm is needed e.g. wide neck aneurysm, multiple filling vessels, very large.
Clipping involves a craniotomy and surgical control of the aneurysm. As noted, the ISAT study demonstrated less favourable results compared to coiling, but there is still a definite role for clipping in some scenarios.
Other surgical interventions may also be indicated depending on the exact clinical circumstances e.g an external ventricular drain in the case of obstructive hydrocephalus.
ICU and medical care will include care that is focused on supporting the patient’s physiology and minimising the risk of general complications e.g. VTE, pressure ulcers. This aspect is very important, as with all patients in a critical care environment and should be carefully attended to.
However, there is also a large degree of management of the patient aimed at preventing the development of the many complications of SAH (noted below), particularly that of delayed cerebral ischaemia (DCI).
The traditional medical approach to general ICU management was termed the triple H therapy:
As an overall concept, this is no longer recommended, but some aspects of the care have remained.
A better breakdown of the management goals can be categorised as:
Blood pressure control
Management of fluid balance
Close observation for complications
A very useful acronym for approaching these aspects of care in these patients is the MEND protocol used at Salford Royal Hospital (freely available at www.neuroICU.guru). This refers to: MAP - Clearly define the blood pressure targets Euvolaemia - careful assessment of fluid balance, aiming for euvolaemia Neurology - regular assessment of neurological status to detect complications Dilate - the use of recognised vasodilator therapy, primarily nimodipine.
Blood Pressure Control
There are two aspects to this, depending on whether the culprit aneurysm is protected.
Before the aneurysm is protected (i.e. coiled or clipped) there is a risk from hypertension as it can result in rebleeding. It is primarily the systolic blood pressure (SBP) value which is the issue here, and a recommended maximum value is 180 mmHg. If the SBP is higher than this, there should be prompt and aggressive control with antihypertensive therapy. The need for rapid but not excessive control really requires titration of an infusion, and labetalol is an ideal first line therapy.
After the aneurysm is protected, this concern goes away and the focus of therapy shifts to maintaining a high mean arterial pressure (MAP)to optimise cerebral perfusion. A cerebral perfusion pressure (CPP) should be calculated and MAP guided by this. This will depend on the clinical picture but a CPP of 60 mmHg is generally the minimum acceptable value. Vasopressors may be indicated to achieve this, but there is a strong link between BP control and volume status and the two have to be considered together. Excessive vasopressor use is inappropriate and may impair cerebral perfusion if the patient is underfilled. In general, hypertension should not be treated in these patients unless it is causing clear complications on another organ system e.g cardiac failure. Indeed, it may represent an endogenous response to DCI, with the body trying to overcome the vasospasm.
Getting the right fluid balance in all critically ill patients is both challenging and important, but even more so in those patients with aSAH. The concept of hyPERvoleamia (as part of the HHH approach) came about because of the detrimental effects of hyPOvolaemia in this patient group. As it is a clinical state with high levels of circulating catecholamines (with a vasoconstrictive tendency) and the whole purpose of medical management is to optimise blood flow to the brain tissue to prevent secondary injury, hypovalemia has a significant potential to impair blood flow to the brain. This is compounded by the potential for natriuresis and diuresis to occur as a result of the pathology (e.g. diabetes insipidus) or management (e.g. noradrenaline). Patients are also commonly hypovolaemic at presentation, and need fluid replenishment. However, excess fluid therapy has the associated cardiovascular/respiratory risks associated with it, and this harm must be balanced against the fact that there is no good evidence for a hypervolaemia strategy.
As such, a euvolaemic status is targeted, with a preference for slightly hypervoleamic rather than hypovolaemic. Simple measurement of input/output can commonly result in a hypovolaemic balance, so a slightly positive target of up to 500ml is the goal, using a combination of feed and balanced crystalloids. Preferably, a goal directed fluid therapy regime is used, with some form of cardiac output monitoring, depending on local resources and skills. This could be FICE or continuous monitoring via arterial waveform analysis etc.
Nimodipine This is a calcium channel antagonist that is thought to have some selectivity for the cerebral circulation. It is the only treatment with clear evidence of a benefit on outcome, by reducing the morbidity from delayed cerebral ischaemia in patients with aSAH, as well as the incidence of DCI occurring. There is also a suggestion of reduced rates of rebleeding. Its mechanism of action is unclear but is thought to relate to reduced smooth muscle calcium levels and therefore reduced vessel wall contraction. It is usually given prophylactically to every patient for 3 weeks following aSAH, as it is difficult to stratify a particular risk group which would benefit more. The dose of 60mg 4 hourly orally, and the oral route is the treatment approach with the only real strong evidence. It can also be given IV in established vasospasm, at a dose of 0.1-1mcg/kg/hr, and continued for 5-14 days. However, there is no good evidence for this and isn’t clearly recommended. Side effects are uncommon, but is mainly related to hypotension (about 2% of patients).
The 2007 Cochrane review provided some useful values of this benefit. It suggests a relative risk ratio for poor outcome of calcium antagonists as a whole to be 0.81 (CI 0.72-0.92) with a NNT of 19. For oral nimodipine alone, the RR was 0.67 (CI 0.55-0.81). They note that, given some of the weaknesses of the data, the benefit is not completely beyond doubt, but the risk vs benefit strongly favours giving it routinely.
Magnesium This had been postulated as having a similar benefit to nimodipine through its calcium antagonism effects. Indeed it has a proven use in pre-eclampsia which is thought to have some similarities in pathophysiology. The 2007 Cochrane review hinted at this benefit, especially when combined with nimodipine, giving a RR of 0.75 (CI 0.57-1.00) for poor outcome. However, it only included 3 trials with 379 patients.
However, the MASH-2 study was a large multicentre RCT that looked at the role of supplemental magnesium vs placebo, in addition to nimodipine treatment. It recruited 1203 patients and showed no difference in outcome, as defined by the modified Rankin scale at 3 months post SAH.
In general, management is now primarily focused on maintaining normal magnesium levels.
Statins There were previously thoughts that statins could play a role in protecting against the inflammatory/excitatory response to SAH that caused problems. Initial data were equivocal, but the Simvastatin in aneurysmal subarachnoid haemorrhage (STASH) trial showed no evidence of benefit and their use is not recommended. However, if a patient is already on a statin, then it is common practice to continue them.
The neurology of the patient needs very close observation to detect for the development of complication, particularly DCI. This requires regular medical examination, looking for even subtle changes in level of consciousness, motor power, speech or behaviour. If ICP monitoring in place then any rises must be quickly assessed.
Complications following SAH include:
Vasospasm/Delayed cerebral ischaemia
Neurogenic pulmonary oedema
This occurs in about 20% of cases of SAH, usually within the first 24 hours, but up to 7 days later. It is usually a result of obstruction to CSF flow by blood clot. It usually presents as alteration in mental state, and an urgent CT scan is indicated in these cases. If detected on CT scan, urgent ventriculostomy is needed.
Late hydrocephalus can also occur from alterations in CSF reabsorption following a SAH (usually after the 10 day mark).
Delayed Cerebral Ischaemia
Vasospasm is the radiographic diagnosis, where narrowing of the cerebral vessels is visualised. Delayed cerebral ischaemia (DCI) is any neurological deterioration for longer than 1 hour that is thought to be related to ischaemia. This is the most important complication of aneurysmal SAH and is the leading cause of death and disability. Pathophysiologically, it can be considered as large capacitance vessel narrowing from arterial smooth muscle contraction, with resulting ischaemia. This is from increased vasoconstrictor activity from the free oxyhaemoglobin that has been released, and increased calcium levels locally may play a role. DCI occurs in up to 30% of patient with aSAH, although radiological visible vasospasm can actually be seen in 70% of patients (hence the importance in the definition).
It can occur between 3 and 15 days, usually with a peak onset around the 7 day mark. It will usually settle spontaneously by 21 days.
There are some well recognised risk factors:
Radiological grade of severity (i.e. the amount of blood and its location)
There isn’t an impact from the way it was managed (clipping vs coiling). The volume of intracranial blood is quite a strong predictor, and in the case of large volumes some vasospasm is almost certain. Blood in the basal cisterns is also a risk factor.
Detection requires close monitoring, which can be particularly challenging if patients are ventilated. If they aren’t, then the presentation will often be of an acute neurological change. Changes which my herald DCI in sedated and ventilated patients include:
A CT scan may be the initial investigation if the cause of the deterioration is uncertain, but the gold standard imaging is conventional angiogram, as it also allows treatment. A CT or MR angiogram may also be used and have fairly similar sensitivity.
Much of the prophylactic measures discussed in the management of SAH are to prevent this complication arising. Oral nimodipine is the prophylactic treatment with the strongest evidence.
The treatment of suspected DCI primarily involves induced hypertension. An urgent neurosurgical opinion is also essential. Induced hypertension involves ensuring optimisation of volume status and cardiac output, alongside targeted elevation of MAP. Cardiac output monitoring is almost always needed to ensure volume status has been optimised, prior to increasing vasopressor treatment to drive up the MAP. A stepwise approach has been described for this, targeting resolution of the symptoms/signs of DCI:
Increase MAP by 10% baseline or target 95 mmHg
Increase MAP by 20% baseline or target 110 mmHg
If these interventions fail, invasive neurosurgical procedures may be needed. Examples include: therapeutic CSF drainage, balloon angioplasty.
Seizures occur in between 1 and 7% of cases of SAH. If they occur following the initial bleed, it may be the result of a rebleed. They should be treated aggressively because of the adverse secondary effects they cause. However, antiepileptic prophylaxis has been associated with worse outcomes and so is not done routinely.
This is challenging but has commonly involved the use of the aforementioned grading systems. A commonly used outcome measure is the Glasgow Outcome Score (GOS) which essentially describes the functional state of the patient at that particular point in time. The outcomes range from dead, through lessening levels of disability up to a good recovery where a return to work is possible. There is also an extended GOS with extra gradations between the levels of disability.
One large study reported the odds of a patient having a ‘good outcome’ on the GOS at 3 months based on their WFNS grade. The likelihood ratios were:
Links & Resources
Bersten A, Soni N. Oh’s intensive care manual (7th ed). 2014
Beers M et al. The Merck manual of diagnosis and therapy (18th ed). 2006.
Perry, J et al. Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. BMJ. 2011. 343:d4277. Available at http://www.bmj.com/content/343/bmj.d4277
Perry J et al. Clinical Decision Rules to Rule Out Subarachnoid Hemorrhage for Acute Headache. JAMA. 2013;310(12):1248-1255.
Mees S et al. Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial. Lancet. 2012. 380;44-49 Available at: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60724-7/abstract?rss=yes
Molyneux A et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005. 366;809-817.