Hypertension (HTN) is the most important and prevalent of the risk factors for ICH, leading to a form of vasculopathy termed lipohyalinosis. Nonmodifiable risk factors include advanced age, male gender, and African American race and Japanese ethnicity.^1-4 Additionally, cerebral amyloid angiopathy (CAA), although usually asymptomatic, is an important risk factor for primary ICH in elderly patients. CAA is characterized by the deposition of β-amyloid protein in small- to medium-sized blood vessels of the brain and leptomeninges, which may undergo fibrinoid necrosis as seen in chronic HTN. Other risk factors include cocaine use, low cholesterol levels, oral anticoagulants, and excessive alcohol abuse.^2,5-14

The diagnosis of ICH is suggested by the rapid onset of neurologic dysfunction and signs of increased intracranial pressure (ICP), such as headache, vomiting, and decreased level of consciousness. The symptoms of ICH are related primarily to the etiology, anatomic location, and extension of the expanding hematoma. Abnormalities in the vital signs such as hypertension, tachycardia, or bradycardia (Cushing response) and abnormal respiratory pattern are common effects of elevated ICP. Confirmation of ICH cannot be based solely on the clinical examination and requires the use of an emergent CT scan (see Figure 2-1) or magnetic resonance imaging, which will differentiate between ischemic and hemorrhagic strokes. The CT scan rapidly evaluates the size and location of the hematoma and its extension into the ventricular system, hydrocephalus, the degree of surrounding edema, and anatomic disruption.⁴ Hematoma volume may be easily calculated from CT scan images by use of the ABC-2 method, a derived formula from the calculation of the volume of the sphere.^10,11 CT angiography (CTA) is not routinely performed in most centers, but may prove to be helpful in predicting hematoma expansion, outcome, and etiology.^15,16

Hematoma growth is an important cause of early neurologic deterioration, and ICH volume is a powerful predictor of the outcome after ICH.^17,18 However, the natural history and prognosis of ICH is not totally dependent on the volume of the hemorrhage.^19,20 An acceptable theory is that an expanding hematoma results from persistent bleeding and/or rebleeding from a single arteriolar rupture. Evidence from studies employing histopathology, CT analysis, single-photon emission computed tomography (SPECT), as well as use of both conventional angiography and CTA suggest that secondary multifocal bleeding into the tissue at the periphery of an existing clot is more likely to occur in those cases of early hematoma enlargement. Analyses of brain tissue have indicated the presence of microscopic and macroscopic bleeding in the area surrounding the fatal hemorrhage, perhaps representing ruptured arterioles or venules.²¹

Other studies employing simultaneous CT and SPECT analyses have shown that, in some cases, early ICH growth relates to secondary bleeding in the periphery of the existing clot into ischemic, congested, peri-lesional tissue²². Similarly, the association between early hematoma growth and irregular clot morphology, which may reflect multifocal bleeding, has been reported. In these studies, the incidence of hematoma growth was greater in patients with irregularly shaped hematomas compared with those with round hematomas, and it was postulated that the irregular shape indicated bleeding from multiple arterioles.^23,24 In one study involving CTA immediately after ICH, the presence of active contrast extravasation into the hematoma was associated with subsequent hematoma enlargement²⁵ and an increase in mortality rate¹⁵ in 30% to 46% of patients.

Finally, bleeding from single and simultaneous bleeding from multiple lenticulostriate arteries have been demonstrated angiographically immediately after ICH.²⁶ In a prospective study of 39 patients with spontaneous ICH, focal enhancing foci (contrast extravasation, “spot sign”) seen in initial CTA were associated with the presence and extent of hematoma progression with good sensitivity (91%) and negative predictive value (NPV, 96%).²⁷

Additionally, this patient was taking warfarin after mechanical valve replacement and AF. In the general population, warfarin increases the risk of ICH by 5- to 10-fold,¹³ and ICH in the setting of anticoagulation carries the worst prognosis.²⁸ Patients receiving oral warfarin should be treated immediately with fresh-frozen plasma (FFP) or prothrombin-complex concentrates (PCCs) and vitamin K (Table 2-1). At least 8 units of FFP (15-30 mL/kg)²⁹ is required to immediately reverse the coagulation defect, but the associated volume load may exacerbate chronic conditions such as cardiac or renal disease.³⁰ High doses of intravenous vitamin K can fully reverse warfarin-induced anticoagulation, but the effect may take up to 12 to 24 hours, during which time the ICH may continue to enlarge. A potential risk of anaphylaxis exists with IV vitamin³¹; therefore, infusion should be done slowly with attention to signs of allergic reaction. PCCs, which consist of the vitamin K–dependent coagulation factors II, VII, IX, and X, may normalize the INR more rapidly than infusion of FFP or vitamin K alone in patients with ICH.^30,32

An alternative to conventional warfarin anticoagulation reversal is the recombinant activated factor VII (rFVIIa, NovoSeven, Novo Nordisk A/S Copenhagen, Denmark).³³ Recombinant activated factor VIIa has been used to reverse warfarin-induced ICH,^33,34 but should be used in conjunction with FFP, PCCs, and vitamin K, as rFVIIa corrects only the warfarin-induced deficit of factor VII, whereas PCC, FFP, and vitamin K correct the deficits in all of the vitamin K–dependent coagulation factors.³⁰ Heparin or low-molecular-weight heparin–induced anticoagulation should be reversed with protamine sulfate,³⁵ and patients with thrombocytopenia or platelet dysfunction can be treated with a single dose of desmopressin (DDAVP: 1-deamino-8-d-arginine vasopressin), platelet transfusions, or both (see Table 2-1).³⁶

No. Based on the results of the recently published phase III FAST trial, routine use of rFVIIa as a hemostatic therapy for all patients with ICH within a 4-hour time window cannot be recommended.

A rapidly deteriorating patient requires optimization of his or her airway, breathing, circulation (ABC), and a thorough laboratory panel should be obtained including hematologic, biochemical, and coagulation profiles; electrocardiogram; and chest radiographs.

Airway Management, Breathing, and Circulation

The rapid deterioration in this patient’s neurologic status mandates securing the airway. Failure to recognize imminent airway loss may result in complications, such as aspiration, hypoxemia, and hypercapnia. Preferred induction agents for rapid-sequence intubation (RSI) in the setting of suspected ICH include propofol³⁷ and etomidate,³⁸ although etomidate has fewer hemodynamic side effects and does not cause an abrupt drop in blood pressure. Both agents are short acting and should not obscure the neurologic examination for a prolonged period of time. In certain circumstances such as this one, neuromuscular paralysis may be needed as part of RSI. Succinylcholine is the most commonly administered muscle relaxant owing to its rapidity of onset (30-60 seconds) and short duration (5-15 minutes).³⁹ However, succinylcholine should be avoided in patients with renal disease because of the rare risk of life-threatening hyperkalemia; furthermore, succinylcholine causes theoretical elevation in the ICP in patients with intracranial mass lesions.^38,40 For this reason, in neurologic patients, nondepolarizing neuromuscular blocking agents such as cis-atracurium (preferred in renal disease), rocuronium,³⁸ or vecuronium are recommended.⁴¹ In patients with increased ICP, premedication with lidocaine for RSI is frequently performed, although this practice is of questionable use.⁴²

Hypertension as well as hypotension should be immediately addressed to decrease hematoma expansion and to maintain adequate cerebral perfusion pressure. Isotonic fluid resuscitation and vasopressors may be indicated in patients who are in shock.⁴³ Dextrose-containing solutions should be avoided because hyperglycemia may be detrimental to the injured brain.⁴⁴

Blood Pressure Control

Extreme levels of blood pressure after ICH should be aggressively but carefully treated to reduce the risk of hematoma expansion and to keep and maintain cerebral perfusion pressure (CPP = mean arterial pressure [MAP] – ICP). Controversy exists about the initial treatment of hypertension in patients with ICH. An expanding hematoma may result from persistent bleeding and/or rebleeding from a single arteriolar rupture. Some studies have reported evidence of hematoma growth from bleeding into an ischemic penumbra zone surrounding the hematoma, but other reports have not confirmed the existence of ischemia at the hypo-perfused area in the periphery of the hematoma.^45,46 In one study, no association was demonstrated between hematoma growth and blood pressure levels, although the use of antihypertensive agents may have negatively confounded this association,⁴⁷ and interestingly, the initial blood pressure level was not associated with hematoma growth in the Recombinant Activated Factor VII ICH Trial.⁴⁸

On the other hand, aggressive blood pressure reduction after ICH may predispose some patients to an abrupt drop in cerebral perfusion pressure (CPP) and ischemia, which in turn may be accompanied by elevations of ICP and further neurologic damage. Some studies have demonstrated that a controlled, pharmacologically based reduction in blood pressure has no adverse effects on cerebral blood flow in humans or animals.^49,50 The blood pressure level has been correlated with an increase in the ICP and volume of the hematoma, but it has been very difficult to explain whether hypertension is the cause of hematoma growth or is just a response to elevated ICP in the setting of large-volume ICH. Results of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT-I) suggested that early intensive blood pressure reduction was safe and was associated with less hematoma expansion. However, the INTERACT-II study showed that intensive lowering of blood pressure did not result in a significant reduction in death or severe disability after ICH. Nevertheless, the secondary prespecified analysis of INTERACT-II using ordinal scales of the modified Rankin Score suggested that rapid blood pressure lowering to < 140 mm Hg after ICH was associated with improved outcomes. The eligible patients in this study included patients with mild ICH (median GCS, 14; interquartile range [IQR], 12-15) and small ICH volumes (median vol, 11 mL, IQR, 6-20). Therefore, the results cannot be extrapolated to all subpopulations of ICH patients, particularly more severely critically ill ICH patients with comorbidities and larger hematomas.⁵¹ An interim analysis of the Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH) study showed a nonsignificant relationship between the magnitude of systolic blood pressure (SBP) reduction and hematoma expansion, and 3-month outcome was observed.⁵² Whether more aggressive blood pressure reduction after ICH is safe is the subject of the ongoing National Institute of Neurologic Disorders and Stroke (NINDS)–supported ATACH pilot study.⁵³

In general, the American Heart Association guidelines indicate that SBP exceeding 180 mm Hg or MAP exceeding 130 mm Hg should be managed with continuous-infusion antihypertensive agents (Table 2-2).⁵⁴ The use of nitroprusside has drawbacks because this agent may exacerbate cerebral edema and intracranial pressure,⁵⁵ and oral and sublingual agents are not preferred because of the need for immediate and precise blood pressure control. In general, no matter how high the blood pressure is, the MAP should not be reduced by more than 15% to 30% over the first 24 hours.⁴⁹ In the setting of impaired blood flow autoregulation, excessive blood pressure reduction may exacerbate ischemia in the area surrounding the hematoma and worsen perihematomal brain injury.^22,56

Observation in an intensive care unit (ICU) or a similar setting is strongly recommended for at least the first 24 hours because the risk of neurologic deterioration is highest and because the majority of patients with brainstem or cerebellar hemorrhage have a depressed level of consciousness requiring ventilatory support.^57,58 Invasive arterial blood pressure, central venous pressure, and pulmonary artery catheter monitoring are invasive modalities that may be indicated in these patients. An external ventricular drain (EVD) should be placed in patients with a depressed level of consciousness (GCS, < 8), signs of acute hydrocephalus or intracranial mass effect on CT, and a prognosis that warrants aggressive ICU care.⁵⁹ Additional acute physiologic derangements that require aggressive interventions include elevated ICP, hyperglycemia, hyperthermia, electrolyte imbalances, and seizure activity, among others.