Management of cerebral haemorrhage

Intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality, and accounts for about 10–15% of all strokes. Although ICH causes higher mortality than other forms of stroke, over the years there was no proven effective treatment of ICH. Increasing age and arterial hypertension are the most important risk factors for ICH. Sustained hypertension is responsible for more than 60% of ICH cases. ICH remains the least treatable form of stroke and its current treatment is mostly supportive. Early mortality measured at 30 days exceeds 50%. Hematoma volume, presence of intraventricular hemorrhage, and decreased level of consciousness are thought to be the most important predictors of poor outcome after ICH.

Almost all recommendations that can be postulated now for ICH management are at the lowest level of evidence (grade C).

1.    Suspected victims of hemorrhagic stroke should be transported without delay to the nearest hospital providing acute stroke care. Neurointensive care, neuroradiology and neurosurgery services should be available in such hospital (grade C).

2.    CT scan of the head is the most important diagnostic procedure in the initial evaluation of patients with suspected ICH (grade C). MRI is as accurate as CT examination for the detection of acute ICH (grade A), and it may be better for the detection of chronic ICH.

3.    In most cases of hypertensive ICH, intraarterial digital subtraction angiography (DSA) is usually not necessary. CT angiography and MRA are helpful and may obviate the need for cerebral angiography (grade C).  DSA should be considered for selected patients to exclude an AVM, aneurysm, vasculitis, or tumor.

4.    In patients with acute ICH there are a number of general medical problems that need to be solved, regardless of hematoma size and location. General treatment measures include: the maintenance of adequate vital functions (airway, breathing, and circulation), proper fluid and electrolyte balance, temperature control, blood glucose management, normal coagulation status, treatment of increased intracranial pressure (ICP), control of arterial hypertension, and prevention of medical complications. Oxygenation is recommended to maintain arterial PO2 between 100 and 150 mm Hg (grade C). Intermittent pneumatic compression devices are indicated to prevent DVT and pulmonary embolism. Indwelling urinary catheter (if used) should be removed within the first few days. Oral feeding should be avoided in the first 24 hours. Gastro-intestinal prophylaxis is recommended to prevent stress ulceration in the acute phase of ICH. Endotracheal intubation is performed in patients in coma, with respiratory failure, and to provide the airway protection (grade C).

Systolic blood pressure (SBP) should be kept at least below 180 mm Hg and mean arterial pressure (MAP) should be lower than 130 mmHg (grade C). In cases with invasive ICP monitoring, a CPP should be maintained at the level >70mm Hg and adjusted treatment of BP is recommended.

There is no need for routine anticonvulsant treatment. Seizures should be treated, however, after the first occurrence.

5.    Specific treatment of ICH is still controversial. As yet, an advantage of neurosurgical intervention over medical treatment has not been established.

In the past, there has not been any RCT on medical treatment for spontaneous ICH.

Recently, three RCTs evaluating new strategies for the treatment of the ICH have been completed.

a.     Early surgery versus initial conservative treatment in patients with spontaneous supratentorial ICH (The International STICH trial);

b.    Stereotactic aspiration combined with instillation of fibrynolitic agent (The SICHPA trial);

c.    Ultra-early haemostatic therapy by using the recombinant activated factor VIIa (The Novo-7 trial)

5.1. Main results of STICH trial

There is no evidence of an overall benefit of early surgery when compared to initial conservative treatment. One finding in a predefined subgroup, that patients with superficial hematomas might benefit from surgery (craniotomy), needs further exploration.

         5.2. The result of SICHPA trial

The trial was prematurely stopped because of low recruitment. A cautious conclusion could be made that stereotactic aspiration of supratentorial hematoma after instillation of a plasminogen activator can be performed safely. It may reduce the hematoma volume significantly.

         5.3. Main results of Novo-7 trial

This was a phase IIb trial which included 400 patients with acute ICH.

Treatment with rFVIIa within 4 hours reduced hematoma expansion, decreased mortality, and improved clinical outcome significantly, despite slight increase in the risk of thromboembolic events. A phase III trial is needed to confirm the beneficial effect of rFVIIa in acute ICH.

         6.    Further statements regarding surgical evacuation (all grade C):

a.     In cerebellar hemorrhage > 3cm in diameter with hydrocephalus, neurological deterioration or brainstem compression, surgical evacuation should be performed urgently.

b.    Intraventricular ICH plus hydrocephalus should be treated with ventricular drainage.

c.    In supratentorial hemorrhages consider removal of clots if there is deterioration from GCS 9 – 12, or if ICP rises by craniotomy if superficial (within 1 cm of cortical surface) by aspiration if deep (more trials needed)

Bibliography

1.     Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, Karimi A, Donald M, Shaw M, Barer DH for the STICH investigators:  Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial

Lancet 2005, 365, 387-397

2.     Mayer SA: Ultra-early hemostatic therapy for intracerebral hemorrhage. Stroke 2003, 34, 224-229

3.     Teernstra OPM, Evers SMAA, Lodder J, Leffers P, Franke CL and Blaauw G: Stereotactic treatment of Intracerebral Hematoma by means of a plasminogen activator. A multicenter randomized controlled trial (SICHPA). Stroke 2003, 34, 968-974

4.     Kidwell CS, Chalela JA, Saver JL et al.: Comparison of MRI and CT for detection of acute ICH. JAMA 2004, 292, 1823-1830

5.     Ohwaki K, Yano E, Nagashima et al.: Blood pressure management in acute ICH. Relationship between elevated blood pressure and hematoma enlargement. Stroke 2004, 35, 1364-1367

6.     Schellinger PD, Fiebach JB, Hoffmann K et al.: Stroke MRI in intracerebral hemorrhage. Is there a perihemorrhagic penumbra? Stroke 2003, 34, 1674-1680

7.     Broderick JP, Adams HP, Barsan W et al.: Guidelines for the management of spontaneous intracerebral hemorrhage. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1999, 30, 905-915

8.     Mayer SA, Brun NC, Broderick J et al.: Safety and feasibility of recombinant factor VIIa for acute intracerebral hemorrhage. Stroke 2005, 36, 74-79

9.     Mayer SA,  Brun NC, Begtrup K et al., for the Recombinant Activated  Factor VII Intracerebral Hemorrhage Trial Investigators: Recombinant Activated Factor VII for Acute Intracerebral Hemorrhage. NEJM 2005, 352, 777-785