Special Feature
Primary Spontaneous Intracerebral Hemorrhage
Uday B. Nanavaty, MD, Pulmonary and Critical Care Medicine, Rockville, Maryland, is Associate Editor for Critical Care Alert.
Intracerebral hemorrhage is defined as extravasation of blood into the brain parenchymal tissue or ventricles. This form of hemorrhage may be primary (as in hypertension or amyloid angiopathy) or it can be secondary to vascular lesions or coagulopathy, or trauma or tumor. Although not the most common variety amongst all patients with stroke, this is the most debilitating and often lethal form of stroke with highest morbidity and mortality rates. Conservative management is appropriate in most patients with small supratentorial location of hemorrhage. A selected group of patients may benefit from life saving surgery. A recent study suggests that in a select group of patients, activated Factor VII may reduce the rate of hematoma expansion. Like most other medical disorders, prevention, unfortunately out of the control of the critical care provider in this case, is the key to reducing morbidity and mortality from this condition.
Introduction: The Hypertensive Bleed1
Acute Intracerebral Hemorrhage (ICH) is a devastating condition that affects patients of all ages and unfortunately results in high morbidity in the survivors and remains a highly lethal disease with mortality rates as high as 25-50%, depending on the inclusion criteria used in the studies. Up to 80% of patients with acute ICH have pre-existing hypertension as the only cause of their condition. These patients are often referred as the Primary ICH or Hypertensive Bleed, and this review will be restricted to this largest group of patients with ICH. Other etiologies of ICH include vascular malformations, trauma, surgery, bleeding into tumors; severe coagulopathy, and others, but these will not be discussed here.
Uncontrolled hypertension of any duration or long standing history of hypertension can be found in all the patients with hypertensive bleed. A genetic basis is being looked into that may help identify groups of patients with hypertension who are likely to develop ICH. Smoking and excessive alcohol use are two known and easily modifiable risk factors. Drug abuse, especially cocaine abuse, can contribute to bleeding in hypertensive patients. Low cholesterol has been identified as a risk factor for ICH as well.
The exact etiology of ICH in hypertensive patients is not clear. It is postulated that uncontrolled blood pressure results in structural changes in several well defined areas of the brain. These areas, especially the thalamus and basal ganglia, pons and cerebellum, comprise the most common areas of the brain where hypertensive ICH develops. Some patients may develop large lobar hemorrhage or an extension into the ventricles of the brain, and others may have small hematoma in other areas of brain as well.
Diagnosis
The clinical picture of headache, nausea and vomiting associated with altered mental status, with or without seizures, is usually seen in of patients with ICH. Depending upon the site and extent of bleeding, patients may present with just headache or focal weaknesses, to pure sensory deficits, or the presenting symptom may be a state of unresponsiveness especially in large lobar hemorrhages. Patients with infratentorial bleeding may present with slurred speech or other facial findings and can have rapid deterioration in consciousness.
Cushing’s triad of hypertension, bradycardia and respiratory irregularities can be seen in patients with cerebral herniation. Hypertension of varying degrees is universal in patients with hypertension-related ICH. Seizures, either convulsive or nonconvulsive, can develop. Focal deficits on neurological examination vary depending upon the location of the lesion. The Glasgow Coma Scale helps in management of these patients and it is useful for predicting overall prognosis.
A non contrast CT scan is the best rapid diagnostic tool available to most critical care physicians in the United States. Not only does it establish the diagnosis, but it also provides important prognostic information. Volume of hematoma from ICH can be accurately measured and provides useful information for management and it should become routine in evaluating ICH. Using CT scan to estimate the volume of ICH (0-29 cm3, 30-60 cm3, and > 61 cm3) and Glasgow Coma Scale (9 or more, 8 or less), Broderick et al2 showed that 30 day mortality can be predicted with 96% sensitivity and 98% specificity. Location of hematoma and extent of edema or intraventricular extension with hydrocephalus may help decisions for surgical intervention as well.
Magnetic resonance imaging (MRI), especially with MR angiography (MRA) may provide greater details about perfusion around the hematoma and may be valuable in detecting vascular malformations or tumors, MRI is time-consuming and hence CT scan remains the diagnostic tool of choice in emergency situations.
Critical Care Management1,3,4
Patients with ICH should be evaluated rapidly and admitted to ICU for monitoring their neurological status and management of their medical problem. Routine blood tests should be performed looking especially for bleeding tendencies and electrolyte abnormalities.
The frequency of neurological assessment remains unclear but traditionally, for the first 24 hours, patients should have bedside neurological assessment every hour. In part, this practice stems from the concept of hematoma expansion, which may develop in as much as a third of the patients. Hematoma expansion is rare after the first 24 hours. The frequency of neurological assessments thereafter depends upon the patient’s medical condition.
Patients with ICH, especially those with infratentorial bleeding, may require intubation for protection of the airway as well as sometimes for acutely lowering intracranial pressure (ICP). When intubating patients with ICH, drugs with unclear effects on ICP should be avoided. Midazolam theoretically increases ICP, and paralytics may result in significant elevation of carbon dioxide, so that these agents should be avoided. Similarly, cough should be avoided and if desired, intravenous lidocaine can be used to reduce cough reflex during intubation. Based on traumatic brain injury data, it is suggested that patients with Glasgow Coma Scale scores less than 8 should be considered for elective intubation in order to avoid aspiration pneumonia.
The patients with ICH often have hypertension that may not be well controlled. It is suggested that blood pressure should be controlled to avoid further bleeding. However, ICH itself leads to hypertension and too low a blood pressure is considered harmful as well. Although no large controlled trials are available, most centers attempt to keep mean arterial pressure less than 125-130 mm Hg. Labetolol or esmolol are commonly used for controlling blood pressure. Nitroprusside and hydralazine should be avoided because of their effects on cerebral blood flow.
Intravenous fluids, isotonic and without glucose, should be administered to maintain euvolemia. Hyperglycemia is detrimental to damaged brain tissue and it is an independent marker of poor outcome in patients with ICH. Therefore, attempts should be made to maintain euglycemia. However, very high blood sugars should be corrected slowly and hypoglycemia should be carefully avoided.
The incidence of seizures in primary ICH is variable. Although older guidelines suggest routine prophylaxis for seizures for 1 month, the practice is variable. Most centers use seizure prophylaxis only if seizures have been noted.
Temperature should be aggressively controlled as fevers are detrimental to injured brain. Acetaminophen and cooling blankets are the most common methods used.
Prophylaxis against deep venous thrombosis should be started upon admission. If heparin is used, caution should be applied to avoid bleeding tendency. Patients with ICH should also receive ulcer prophylaxis as they are at high risk of developing stress ulcers and gastrointestinal hemorrhage. The head end of the bed should be kept elevated in most patients to at least 30 degrees to minimize and prevent aspiration.
If patients demonstrate signs or symptoms of increased ICP, ventriculostomy should be considered for both monitoring and treatment purposes. If ICP monitoring is available, ICP should be kept below 20 mm Hg, and cerebral perfusion pressure should be maintained > 70 mm Hg. To lower ICP acutely, one may use hyperventilation to maintain arterial PCO2 in the 25-30 mm Hg range. Further ICP lowering can be achieved by administering mannitol (0.25-1 g/Kg) intravenously every 4 to 6 hours. Mannitol should be infused slowly and serum osmolality should be monitored to avoid a severe hyperosmolar state. It is recommended that serum osmolality be maintained in the 300-310 mOsm/L range. Steroids are detrimental in ICH associated cerebral edema and should be avoided. If ventriculostomy is available, draining CSF may be an easy way to reduce ICP. Rarely, medications such as ramifentanyl or thiopental may be necessary to reduce ICP, especially in agitated patients.
Surgical Options
The role of early surgical evacuation of hematoma in ICH is debatable. Patients with hematoma-induced obstructive hydrocephalus may benefit from ventriculostomy and drainage. Eventually, they may need a shunt procedure. Patients with cerebellar hematoma, especially if the hematoma is greater than 3 cm in size or with neurological deterioration, benefit from surgical evacuation, which is often considered a life saving procedure. Similarly, patients with supratentorial hematoma with midbrain extensions may benefit from surgery. Young patients with large cortical hematomas that are easily accessible are considered for surgical treatment options as well. The role of routine evacuation of hematoma in supratentorial locations, however, is not clear.
Recent Advances
Two recent publications have shed light on the role of medical and surgical therapies in ICH. In a landmark trial of medical therapy in ICH, Mayer et al5 have shown that early in the course of patients with ICH, even with exclusion of coagulopathy, injection of activated Factor VII results in significant reduction in the rate of hematoma expansion. This study included patients with primary spontaneous intracerebral hemorrhage within four hours of their onset. In a placebo-controlled trial, it was shown that 3 doses of activated Factor VII were effective in reducing the rate of hematoma expansion from estimated mean expansion of 29% in the placebo group to 14% in a combined group of patients receiving 3 doses of activated Factor VII.
Although the authors also concluded that mortality was reduced, the study was not powered to detect mortality differences and no statistical methods were used to adjust for multiple comparisons. There was a significant increase in thromboembolic events in the treatment group such that any history of thromboembolic disease, such as deep venous thrombosis, pulmonary embolism, acute myocardial infarction, or transient ischemic attacks or stroke is a contraindication to using activated Factor VII. One can hope that some day there will be a trial of activated Factor VII in spontaneous ICH to see if mortality can truly be affected. Unfortunately, this study had some imbalance in the Glasgow Coma Scale score in the placebo group (range, 3-15) and treatment groups (6-8 to 15). For this reason, I would not consider the mortality benefit significant in spite of the authors’ claims to the same.
In another landmark trial, called STICH6 (surgical trial in ICH) investigators suggested that early evacuation of hematoma in patients with ICH of greater than 2 cm size in supratentorial location did not alter the outcome. This trial excluded patients with cerebellar hemorrhage or those with supratentorial hematoma with extension into the brainstem. They also excluded patients with Glasgow Coma Scale scores of less than 5, where the prognosis is grim. With more than 1000 patients in the trial, the study failed to show any significant benefit of early evacuation of hematoma. One of the main inclusion criteria in the STICH study was that the neurosurgeon involved was unsure of benefit of surgery in the given patient. Thus, when in doubt, conservative treatment without surgical intervention remains a good choice.
Prognosis
Outcome of ICH is dependent upon the volume of blood in the parenchyma and to a certain extent on the Glasgow Coma Scale score. Patients with Glasgow Coma Scale scores of less than 4 have poor outcomes, except perhaps those patients who have cerebellar hematomas and can have surgical evacuation. Young patients can occasionally survive large lobar hematomas. Only about a quarter of all patients with ICH can regain functional independence, and mortality remains in the 30% range even in selected groups of patients, even under study conditions, where moribund patients are often excluded.
References
- Broderick JP, et al. Stroke. 1999;30:905-915.
- Broderick JP, et al. Stroke. 1993;24:987-993.
- Manno EM, et al. Mayo Clin Proc. 2005;80(3):420-433.
- Rincon F, et al. Curr Opin Crit Care. 2004;10:94-100.
- Mayer SA, et al. N Engl J Med. 2005;352:777-785.
- Mendelow AD, et al. Lancet. 2005;365:387-397.
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