Chapter 2: Intracerebral Hemorrhage

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 and Japanese race/ethnicity. ^1-4 Additionally, cerebral amyloid angiopathy (CAA), although usually asymptomatic, is an important risk factor for primary ICH in the elderly. 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 rely solely on the clinical examination and requires the use of an emergent CT scan (see Figure 2-1) or magnetic imaging (MRI) and will differentiate between ischemic and hemorrhagic strokes. The CT scan rapidly evaluates the size and location of the hematoma, extension into the ventricular system, hydrocephalus, 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 (Figure 2-2). ^{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), and both conventional 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 bleeds 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, perilesional tissue ²² (Figure 2-3). Similarly, the association between early hematoma growth and irregular clot morphology, which may reflect multifocal bleeding, has been reported, and 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 enlargement ²⁵ and an increase in mortality rate ¹⁵ 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 and 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%) (Figure 2-4). ²⁷

Additionally, this patient was taking warfarin for 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 reversed immediately with fresh-frozen plasma (FFP) or prothrombin-complex concentrates (PCCs) and vitamin K (Table 2-1). At least 8 units of FFP (15 to 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 vitamin ³¹ ; therefore, infusion should be done slowly with attention to signs of allergy. Prothrombin-complex concentrates, 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 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, while 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 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 rapid deteriorating patient requires optimization of his/her ABCs, and a thorough laboratory panel should be obtained including hematologic, biochemical, and coagulation profiles; electrocardiogram (ECG); and chest radiographs.

Airway Management, Breathing, and Circulation

The rapid deterioration in this patient's neurologic examination 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 propofol 37 and etomidate, 38 although etomidate has less hemodynamic side effects and does not cause an abrupt drop in blood pressure. Both these agents are short acting and should not obscure the neurologic examination for a prolonged period of time. In certain circumstances like 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 to 60 seconds) and short duration (5 to 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 used, although this practice is of questionable use. ⁴²

Hypertension as well as hypotension should be immediately addressed to decrease hematoma expansion and to keep an adequate cerebral perfusion pressure. Isotonic fluid resuscitation and vasopressors may be indicated in those patients in shock. ⁴³ Dextrose-containing solutions should be avoided as 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 hypoperfused 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 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 if hypertension is the cause of hematoma growth or if this 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) suggested that early intensive blood pressure reduction seemed to attenuate hematoma expansion in patients with ICH, ⁵¹ and in an interim analysis of the Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH) study, a nonsignificant relationship between the magnitude of systolic blood pressure (SBP) reduction and hematoma expansion and 3-month outcome was observed. ⁵² If 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 SBPs 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 since 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 beyond 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 ICU or a similar setting is strongly recommended for at least the first 24 hours, since 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 should be placed in patients with a depressed level of consciousness (GCS of 8 or less), 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.

Management of ICH

Large-volume ICH carries the risk of developing cerebral edema and high ICP, and the presence of IVH further increases the risk of mortality ^{60, 61} (see Figure 2-1). This effect is primarily related to the development of obstructive hydrocephalus and alterations of normal cerebrospinal fluid flow dynamics. Patients with large-volume ICH, intracranial mass effect, and coma may benefit from ICP monitoring, although this intervention has not been proved to benefit outcomes after ICH, ^{62, 63} initial cerebrospinal fluid (CSF) drainage may be a lifesaving procedure, particularly in the setting of hydrocephalus and IVH. ⁶⁴ This technique allows for rapid clearance of CSF, improvement of ICP, and ICP/CPP monitoring. As a general rule, an ICP monitor or external ventricular drain (EVD) should be placed in all comatose ICH patients (GCS of 8 or less) with the goal of maintaining ICP less than 20 mm Hg and CPP greater than 70 mm Hg, unless their condition is so dismal that aggressive ICU care is not warranted. Compared to parenchymal monitors, EVDs carry the therapeutic advantage of allowing CSF drainage and have the disadvantage of a substantial risk of infection (approximately 10% during the first 10 days). ⁶⁵

Sedation should be used to minimize pain, agitation, and decrease surges in ICP, and in general, many practitioners prefer sedative agents and nondepolarizing neuromuscular paralytic agents for RSI that do not have effects on ICP such as propofol, etomidate, cis-atracurium, and vecuronium. 37, ^{41, 66} Additionally, this patient's head should be positioned at 30-degree angle to minimize ICP and reduce the risk of aspiration or ventilator-associated pneumonia. In mechanically ventilated patients, the further need for head elevation should be guided by changing pulmonary and volume needs.

Additional advanced techniques for the management of elevated ICP have evolved from the experience in traumatic brain injury. Two different concepts for the management of ICP currently exist. The Lund concept assumes a disruption of the blood-brain barrier (BBB) and recommends manipulations to decrease the hydrostatic blood pressure and to increase osmotic pressures to favor the maintenance of the vascular compartment at the expense of a higher risk of ischemia. ⁶⁷ The other concept, cerebral perfusion pressure (CPP) optimization (CPP = MAP – ICP) favors a maintenance of the CPP of 70 mm Hg or more to minimize reflex vasodilation or ischemia ^{68, 69} at the expense of potentially aggravating ICP. There is no prospective control trial addressing the superiority of either of these two different methods for ICP management after ICH.

Hyperosmolar therapy and hyperventilation should be used after sedation and CPP optimization fail to normalize ICP. ⁷⁰ The initial dose of mannitol is 1.0 to 1.5 g/kg of a 20% solution, followed by bolus doses of 0.25 to 1.0 g/kg as needed to a target osmolarity of 300 to 320 mOsm/kg. Additional doses can be given as frequently as once an hour based on the initial response to therapy with the anticipation of a transient drop in blood pressure (BP). Hypertonic saline (HS), such as 0.5 to 2.0 mL/kg of 23.4% saline solution, can be used as an alternative to mannitol, particularly in the setting of shock and when CPP augmentation is desirable through a central venous line. ⁷¹ Hyperventilation is generally used sparingly in the ICU and for brief periods in monitored patients because its effect on ICP tends to last for only a few hours. Good long-term outcomes can occur when the combination of osmotherapy and hyperventilation is successfully used to reverse transtentorial herniation. ⁷²

For cases of severe or intractable elevated ICP, barbiturates and induced therapeutic hypothermia are also effective tools to control refractory elevated ICP by decreasing cerebral metabolic activity, which translates into a reduction of the CBF, and fall of the ICP. These two techniques require expertise, advanced tools, and continuous monitoring of cerebral electrical activity, and it may be associated with significant complications. ^73-75

Hyperglycemia

Admission hyperglycemia is a potent predictor of 30-day mortality in both diabetic and nondiabetic patients with ICH. ⁷⁶ In ischemic stroke, hyperglycemia occurs in 20% to 40% of patients and is associated with infarct expansion, worse functional outcome, longer hospital stays, higher medical costs, and an increased risk of death, and it is felt to be secondary to a catecholamine surge and generalized stress response. ^77-79 In the critically ill population, hyperglycemia seems much more acutely toxic than in healthy individuals, for whom cells can protect themselves by downregulation of glucose transporters. ⁸⁰ In a recent study, high serum glucose concentrations were related to lower scores on the admission GCS and to unfavorable clinical outcomes, ⁸¹ but episodes of hypoglycemia have also been associated with increased mortality ⁸² and worst outcomes in neurologic patients, ⁸³ even though in strict clinical environments tight glucose control has been linked to reductions in intracranial pressure, duration of mechanical ventilation, and seizure activity in critically ill neurologic patients. ⁸⁴ Thus, to minimize the risk of severe hypoglycemia and to avoid worsening possible neuronal damage related to hyperglycemia, it may be reasonable to have tight sugar control with targets between 100 and 150 mg/dL.

Temperature Control

Fever after ICH is common, particularly with IVH, ⁸⁵ and should be treated aggressively. Sustained fever after ICH has been shown to be independently associated with poor outcomes. ⁸⁶ A large body of experimental evidence indicates that even small degrees of hyperthermia can exacerbate ischemic brain injury ^{87, 88} as brain temperature elevation has been associated with hyperemia, exacerbation of cerebral edema, and elevated ICP. ^{89, 90} As a general standard, acetaminophen and cooling blankets are recommended for all patients with sustained fever in excess of 38.3°C (101^oF) ^{73, 91} despite the lack of prospective randomized controlled trials supporting this approach. Newer adhesive surface-cooling systems (Arctic Sun, Medivance Inc, Lousville, CO, USA) and endovascular heat exchange catheters (Cool Line System, Alsius, Inc, Chelmsford, MA, USA) have been shown to be much more effective for maintaining normothermia ⁹² ; however, it remains to be seen if these measures can improve clinical outcome.

Fluids

Isotonic fluids such as 0.9% saline at a rate of approximately 1 mL/kg per hour should be given as the standard intravenous replacement fluid for patients with ICH and optimized to achieve euvolemic balance and an hourly diuresis of > 0.5 mL/kg. Free water given in the form of 0.45% saline or 5% dextrose in water can exacerbate cerebral edema and increase ICP because it flows down its osmotic gradient into injured brain tissue. ⁴⁴ Systemic hyposmolality (> 280 mOsm/L) should be aggressively treated with mannitol or 3% hypertonic saline. A state of euvolemia should be maintained by monitoring fluid balance and body weight, and by maintaining a normal central venous pressure (range 5 to 8 mm Hg). Careful interpretation of the CVP should be done when analyzing its value in the setting of positive end-expiratory pressure (PEEP). The use of hypertonic saline in the form of a 2% to 3% sodium (50:50 chloride-acetate) solution (1 mL/kg per hour) has become an increasingly popular alternative to normal saline as a resuscitation fluid for patients with significant perihematomal edema and mass effect after ICH. The goal is to establish and maintain a baseline state of hyperosmolality (300 to 320 mOsms/L) and hypernatremia (150 to 155 mEq/L), which may reduce cellular swelling and the number of ICP crises. Potential complications of hypertonic saline use are encephalopathy, subdural hematomas, coagulopathy, fluid overload, hypokalemia, cardiac arrhythmias, and hyperchloremic metabolic acidosis. ⁹³ The serum sodium level should never be allowed to drop more than 12 mEq/L over 24 hours, as rapid withdrawal of hypertonic therapy may result in rebound cerebral edema, leading to elevated ICP and/or herniation syndromes. ^{93, 94}

Prevention of Seizures

Seizures should be treated with intravenous lorazepam (0.05 to 0.1 mg/kg) followed by a loading dose of phenytoin or fosphenytoin (20 mg/kg). Patients with ICH may benefit from prophylactic antiepileptic therapy (AED), but no randomized trial has addressed the efficacy of this approach. The American Heart Association guidelines have recommended antiepileptic medication for up to 1 month, after which therapy should be discontinued in the absence of seizures. ⁴³ This recommendation may be supported by the results of a recent study that showed that the risk of early seizures was reduced by prophylactic AED therapy. ⁹⁵ The 30-day risk for convulsive seizures after ICH is approximately 8%, and the risk of overt status epilepticus is 1% to 2%. ⁹⁵ Lobar location and small hematomas are independent predictors of early seizures. ⁹⁵ The argument for prophylactic anticonvulsant therapy in stuporous or comatose ICH patients is bolstered by the fact that continuous EEG monitoring demonstrates electrographic seizure activity in approximately 25% of these patients despite treatment. ^{96, 97} The risk of late seizures or epilepsy among survivors of ICH is 5% to 27%. ⁹⁵

Deep Venous Thrombosis Prophylaxis

Patients with ICH are at high risk for deep vein thrombosis (DVT) and pulmonary embolism, a potentially fatal complication, due to limb paresis and prolonged immobilization. Dynamic compression stockings should be placed on admission. ⁹⁸ A small prospective trial has shown that low-dose subcutaneous heparin (5000 U bid) starting after the second day significantly reduced the frequency of venous thromboembolism with no increase in intracranial bleeding. ⁹⁹ Treatment with low-molecular-weight heparin (ie, enoxaparin 40 mg daily) is a reasonable alternative if renal function is normal. It is generally safe to initiate the DVT prophylaxis after ICH after the first 24 to 48 hours provided that there is no active bleeding or hematoma expansion in progress nor any underlying coagulopathy.

Nutrition

As is the case with all critically ill neurologic patients, enteral feeding should be started within 48 hours to avoid protein catabolism and malnutrition. A small-bore nasoduodenal feeding tube may reduce the risk of aspiration events.

Several surgical techniques have been studied in ICH patients and are currently under clinical investigation.

Craniotomy and Clot Evacuation

Craniotomy has been the most studied intervention for the surgical management of ICH. Two earlier smaller trials showed that for patients presenting with moderate alterations in the state of consciousness, surgery reduced the risk of death without improving the functional outcome ¹⁰⁰ and that ultra-early evacuation of hematoma improved the 3-month National Institutes of Health Stroke Scale (NIHSS) ¹⁰¹ without effect in mortality rate, but a meta-analysis of all prior trials of surgical intervention for supratentorial ICH showed no significant benefit from this intervention. ¹⁰² The Surgical Trial in Intracerebral Haemorrhage (STICH) study, a landmark trial of over 1000 ICH patients, showed that emergent surgical hematoma evacuation by craniotomy within 72 hours of onset fails to improve outcome compared to a policy of initial medical management. ¹⁰³ In a post-hoc analysis of STICH, the subgroup of patients with superficial hematomas and no IVH had better outcomes in the surgical arm. ¹⁰⁴ This observation provided support for the STICH-II trial, which is currently enrolling patients. In contrast to supratentorial ICH, there is much better evidence that cerebellar hemorrhages exceeding 3 cm in diameter benefit from emergent surgical evacuation, as abrupt and dramatic deterioration to coma can occur within the first 24 hours of onset in these patients. ¹⁰⁵ For this reason, it is generally unwise to defer surgery in these patients until further clinical deterioration occurs.

Emergency Hemicraniectomy

Hemicraniectomy with duraplasty has been proposed as a lifesaving intervention for several neurologic catastrophes such as malignant middle cerebral artery (MCA) infarction and poor-grade subarachnoid hemorrhage (SAH). No randomized controlled trial has been conducted in patients with ICH. In a report of 12 consecutive patients with hypertensive ICH and treated with hemicraniectomy, 92% survived at discharge and 55% had a good functional outcome at discharge. ¹⁰⁶ These preliminary data support the need for better-controlled studies addressing the role of this surgical technique in ICH patients (Figure 2-5).

Minimally invasive surgery (MIS)

The advantages of MIS over conventional craniotomy include reduced operative time, the possibility of performance under local anesthesia, and reduced surgical trauma. Endoscopic aspiration of supratentorial ICH was studied in a small single-center randomized controlled trial. ¹⁰⁷ The study showed that this technique provided a reduction of mortality rate at 6 months in the surgical group, but surgery was more effective in superficial hematomas and in younger patients (younger than 60 years). ¹⁰⁷ Similarly, a report from China evaluated the effects of minimally invasive craniopuncture versus medical therapy in a cohort of 465 patients with basal ganglia ICH. Improvement in neurologic outcome at 14 days and 3 months was better in the treatment group, although no differences were seen in long-term mortality. ¹⁰⁸

Thrombolysis and clot evacuation

Thrombolytic therapy and surgical removal of hematomas is another technique that has been studied in a single-center randomized clinical trial. ¹⁰¹ Patients in the surgical group had better outcome scores than the medically treated group. Finally, a multicenter randomized control trial examined the utility of sterotactic urokinase infusion when administered within 72 hours to patients with GCS score of 5 or more and hematomas 10 mL or more in size, provided a significant reduction in hematoma size and mortality rate at the expense of higher rates of rebleeding but no significant differences in outcomes measures were seen. ¹⁰⁹

Thrombolysis after IVH

Intraventricular hemorrhage (IVH) commonly results from extension of ICH into the cerebral ventricular system, and is an independent predictor of mortality rate after ICH. ²⁰ Intraventricular administration of the plasminogen activator urokinase every 12 hours may reduce hematoma size and the expected mortality rate at 1 month. ¹¹⁰ Several small studies have reported the successful use of urokinase or tissue plasminogen activator (tPA) for the treatment of IVH, with the goal of accelerating the clearance of IVH and improving clinical outcome. ¹¹¹ A Cochrane systemic review published in 2002 summarized the experience of several case series providing evidence of safety but no definitive efficacy. ¹¹² The ongoing Phase III Clear IVH Trial (Clot Lysis Evaluating Accelerated Resolution of Intra Ventricular Hemorrhage) is designed to investigate the optimum dose and frequency of r-tPA administered via an EVD to safely and effectively treat IVH and will soon provide some insight on this issue. When used off-label, a dose of 1 mg of r-tPA every 8 hours (followed by clamping of the EVD for 1 hour) is reasonable until clearance of blood from the third ventricle has been achieved. Doses of 3 mg or more of tPA for IVH thrombolysis have been associated with an unacceptably high bleeding rate (D. Hanley, MD, personal communication, 2004).

The mortality rate of ICH is 35% to 50% at 30 days and 47% at 1 year. ^{60, 113} Factors that consistently predict mortality or adverse outcomes in ICH have been studied extensively. Independent predictors for 30-day and 1-year mortality rates include GCS and/or depressed level of consciousness, age, ICH volume, the presence of IVH, and infratentorial origin. ^{20, 60} A simple clinical grading scale, the ICH score, permits calculation of mortality rate, allowing use of uniform terms and enhancing communication between physicians. Its usefulness has been validated in predicting 30-day mortality rate. ¹⁹ The mortality rates for scores of 0, 1, 2, 3, 4, and 5 are 0%, 13%, 26%, 72%, 97%, and 100%, respectively. Additional factors associated with high mortality rate after ICH include the presence of SAH, wide pulse pressure, history of coronary artery disease, and hyperthermia. ⁶⁰ Factors associated with good outcomes include a low NIHSS score and low temperature on admission. ¹⁹ Restarting anticoagulation in patients with a strong indication, such as a mechanical heart valve or AF with a history of cardioembolic stroke, can be safely implemented after 10 days ¹¹⁴ (Table 2-3).