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1114 SECTION 14: Neurology and vomiting. The presumptive cause is the intermittent obstruction of cerebrospinal fluid flow through the foramina of Monro with associated rapid increase in intracranial pressure.  ACUTE ANGLE-CLOSURE GLAUCOMA Acute angle-closure glaucoma results from obstruction of aqueous humor flow due to narrow anterior chamber angle. This leads to increased intraocular pressure. Peak incidence occurs over age 70, and pupillary dilatation can precipitate an attack. Presentation includes abrupt eye pain, vision changes, and headache, although nausea and vomiting may occur. Decreased visual acuity, mid-fixed dilated pupil, and an edematous cornea may be found on exam. Diagnosis includes ocular pressure greater than 21 mm Hg, although this is usually greater than 30 mm Hg. 113-115  PREECLAMPSIA Preeclampsia may present with headache and should be considered in a female after 20 weeks of gestation up to 6 weeks postpartum with blood pressure greater than 140/90 mm Hg in combination with proteinuria or end-organ damage. Proteinuria is not required for diagnosis, and hypertension with thrombocytopenia, renal insufficiency, impaired liver function, cerebral or visual disturbance, or pulmonary edema is diagnostic.  OTHER CAUSES Other etiologies of headache include sinusitis, Valsalva-associated headache, and coital headache. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Spontaneous Subarachnoid and Intracerebral Hemorrhage Anna M. Nelson Caitlin A. Mase O. John Ma INTRODUCTION Although hemorrhagic strokes, including nontraumatic subarachnoid hemorrhages and intracerebral hemorrhages, account for a relatively small portion of ED visits, a missed diagnosis can produce devastating results. Early recognition and aggressive management may improve outcomes. Hemorrhagic stroke accounts for 15% of all strokes and is classified according to the anatomic location of the bleed; nearly one third of hemorrhagic strokes are the subarachnoid type, whereas two thirds are from intracerebral hemorrhage. Subarachnoid hemorrhage is the leakage of blood into the subarachnoid space and classically presents as a sudden, severe headache. Intracerebral hemorrhage, bleeding into the brain parenchyma itself, typically presents as an acute neurologic deficit, often accompanied by headache. The features and treatment of subarachnoid and intracerebral hemorrhage are discussed in this chapter. Management of intracerebral hemorrhage is very different from the management of ischemic stroke. Ischemic stroke is discussed in Chapter 167, “Stroke Syndromes. ” CHAPTER TABLE 166-1 Risk Factors for Subarachnoid Hemorrhage •   Hypertension •   Smoking •   Excessive alcohol consumption •   Polycystic kidney disease •   Family history of subarachnoid hemorrhage •   Coarctation of the aorta •   Marfan’s syndrome •   Ehlers-Danlos syndrome type IV •    α1-Antitrypsin deficiency  SUBARACHNOID HEMORRHAGE EPIDEMIOLOGY About 75% of atraumatic subarachnoid hemorrhages are caused by a ruptured aneurysm. In about 20% of cases a cause is not identified. 2 The remaining causes are related to a variety of miscellaneous conditions, including arteriovenous malformations, sympathomimetic drugs, and other less common causes. About 20% of patients with one aneurysm will have an additional aneurysm, which makes identification of the initial aneurysm important.

not identified. 2 The remaining causes are related to a variety of miscellaneous conditions, including arteriovenous malformations, sympathomimetic drugs, and other less common causes. About 20% of patients with one aneurysm will have an additional aneurysm, which makes identification of the initial aneurysm important. Two percent of family members of patients with subarachnoid hem orrhage will develop the same disease. This risk rises with increasing number of family members involved or with a family history of adult polycystic kidney disease. 2 Hypertension and smoking increase risk as well. Additional risk factors are listed in Table 166-1. PATHOPHYSIOLOGY Cerebral aneurysms are focal arterial pouches typically located in areas of bifurcation of the circle of Willis. While the precise pathophysiology is not known, many factors have been associated with aneurysmal development and rupture. Such factors include genetic predisposition, cel lular aberrations in vascular wall repair or remodeling, and aberrations in local blood flow. 3 While it is not possible to predict rupture risk of a particular aneurysm, larger aneurysms (>5 to 10 mm) are more likely to rupture than smaller aneurysms. 3,4 CLINICAL FEATURES Patients with subarachnoid hemorrhage classically present to the ED with a severe headache of acute onset (termed a “thunderclap” headache) that reaches maximal intensity within seconds. Typically, the headache persists for several days but may resolve in a shorter period of time. Subarachnoid hemorrhage is diagnosed in 11% to 25% of patients who present to the ED with a thunderclap headache. 5,6 Even if a patient is not experiencing the “worst headache of their life, ” a headache that is different in intensity or quality from past headaches should raise concern for subarachnoid hemorrhage . Headaches associated with loss of consciousness, seizure, diplopia or other neurologic signs, or nuchal rigidity also require clinical investigation. 7 Less frequently, patients may present with nausea and vomiting, altered mental status, photophobia, or symptoms suggestive of ischemic stroke. Approximately 20% of patients develop their symptoms while engaged in activities that cause increased blood pressure, such as exercise, sexual intercourse, or defecation. DIAGNOSIS Consider subarachnoid hemorrhage in the differential diagnosis for all patients presenting with a concerning headache. Subarachnoid hemor rhage can be ruled out with 100% sensitivity with implementation of the Ottawa Subarachnoid Hemorrhage Rule for headache evaluation. Although inclusion criteria are stringent, subarachnoid hemorrhage may be excluded in patients under 40 years of age, without neck pain Tintinalli_Sec14_p1101-1186.indd 1114 8/2/19 12:08 PM

age can be ruled out with 100% sensitivity with implementation of the Ottawa Subarachnoid Hemorrhage Rule for headache evaluation. Although inclusion criteria are stringent, subarachnoid hemorrhage may be excluded in patients under 40 years of age, without neck pain Tintinalli_Sec14_p1101-1186.indd 1114 8/2/19 12:08 PM CHAPTER 166: Spontaneous Subarachnoid and Intracerebral Hemorrhage 1115 causes of headache, such as meningitis or idiopathic intracranial hypertension. The main disadvantage of lumbar puncture includes post–lumbar puncture headache and other discomfort for the patient; a lumbar puncture may be contraindicated in the patient with coagulopathy or thrombocytopenia. The two CSF tests of greatest interest are the presence of xantho chromia and red blood cell (RBC) count. Xanthochromia is a yellow appearance of the CSF due to the enzymatic breakdown of blood releasing bilirubin. Any exposure of the CSF to light prior to interpre tation can increase the rate of bilirubin degradation, which decreases any xanthochromia present. 2 Similarly, a delay in processing the CSF specimen may result in the development of xanthochromia following a traumatic lumbar puncture. CSF is evaluated for xanthochromia with visual inspection, the standard technique in most U.S. laboratories, or by spectrophotometry, which may have superior sensitivity but only 75% specificity, resulting in false positives. 28 The utility of the test is further limited in that it takes approximately 12 hours from hemorrhage onset for xanthochromia to develop in CSF . The RBC count in the third or fourth tube of CSF is commonly used to identify subarachnoid hemorrhage. The number of RBCs that constitutes a positive lumbar puncture result has never been clearly defined, nor has the number of RBCs that may be attributed to a traumatic lumbar puncture. One study demonstrated that approximately 10% to 15% of lumbar punctures are traumatic, using cutoffs of 400 and 1000 RBCs, respectively. 30 A comparison of cell counts between consecutive tubes or between tubes 1 and 4 is sometimes used to differentiate subarachnoid hemorrhage from a traumatic lumbar puncture. One small study, how ever, demonstrated that a 25% reduction in RBCs between tubes 1 and 4 may occur even in cases of confirmed subarachnoid hemorrhage. Another small study found that RBCs <100 in the final tube effectively ruled out subarachnoid hemorrhage, whereas an RBC count of >10,000 TABLE 166-2 Differential Diagnosis of Subarachnoid Hemorrhage •   Vascular pathology (other intracranial hemorrhage, ischemic stroke or transient ischemic attack, arterial dissection, venous thrombosis) •   Drug toxicity •   Infection (meningitis, encephalitis) •   Intracranial tumor •   Intracranial hypotension •   Metabolic derangements •   Primary headache syndromes (benign thunderclap headache, migraine, cluster headache) •   Hypertensive disorders or stiffness, without a witnessed loss of consciousness, without onset during exertion, without a thunderclap headache, and without limited neck flexion. 8-10 Misdiagnosis is associated with normal mental status (present in about half of patients with subarachnoid hemorrhage) and smaller size of hemorrhage. 11 Up until recently, patients were believed to have worse outcomes if misdiagnosed, but this might not always be the case, and a careful evaluation for subarachnoid hemorrhage for patients who cannot be ruled out with the Ottawa subarachnoid hemorrhage rule is still important. 11-14 Complications of missed diagnosis include repeat hemorrhage and obstructive hydrocephalus. Symptomatic improvement following analgesics does not exclude life-threatening causes of headache. 15 Table 166-2 lists the differential diagnosis of subarachnoid hemorrhage.

subarachnoid hemorrhage rule is still important. 11-14 Complications of missed diagnosis include repeat hemorrhage and obstructive hydrocephalus. Symptomatic improvement following analgesics does not exclude life-threatening causes of headache. 15 Table 166-2 lists the differential diagnosis of subarachnoid hemorrhage.  IMAGING The initial diagnostic modality of choice when subarachnoid hemor rhage is suspected is a noncontrast CT of the head ( Figures 166-1 and 166-2). The sensitivity of CT in diagnosing subarachnoid hemor rhage is highest shortly after symptoms begin and is estimated to be 98% within 6 to 12 hours of symptom onset . In patients who are neurologically intact who present with a thunderclap headache, a normal head CT within 6 hours of headache onset is extremely sensi tive in ruling out aneurysmal subarachnoid hemorrhage. 16 Sensitivity decreases to about 91% to 93% at 24 hours and continues to decline rapidly thereafter, reaching 50% at 1 week. 7,15 Newer-generation CT scanners are even more sensitive for detecting subarachnoid hemor rhage, especially in the setting of (1) patients presenting within 6 hours of symptom onset, and (2) greater availability of a timely interpretation by a neuroradiologist. 17-19 CT angiography and MRI or magnetic resonance angiography are options after a negative head CT, when these studies are clinically appropriate and available. 20 In a small study, two of 116 patients had an aneurysm discovered by CT angiography after normal findings on both CT and lumbar puncture. 21 The probability of correctly excluding a subarachnoid hemorrhage following CT/CT angiography is about 99.4%. 22 One of the consequences of this diagnostic pathway is the detection of incidental aneurysms that may prompt unnecessary intervention, with the background incidence of aneurysms in the population (2% to 6%) exceeding that of the morbidity and mortality associated with subarachnoid hemorrhages, as well as the ionizing radiation. 23 Current clinical practice has moved toward ruling out subarachnoid hemor rhages in patients with a normal CT/CT angiography so long as they present within 6 hours of symptom onset. The option for obtaining a lumbar puncture in patients in whom there is still a strong suspicion of subarachnoid hemorrhage, despite negative imaging studies, remains a method for complete evaluation. The usefulness of MRI, particularly fluid-attenuated inversion recovery MRI sequences, is limited. 24 A negative MRI result still needs to be followed by a lumbar puncture.25  LUMBAR PUNCTURE Most authorities recommend cerebrospinal fluid (CSF) analysis when a patient with suspected subarachnoid hemorrhage has a normal head CT. 26,27 Another advantage of lumbar puncture is the ability to identify other FIGURE 166-1. Diffuse subarachnoid hemorrhage with associated ventricular hemor rhage. Top arrow indicates blood in interhemispheric fissure. Bottom arrow indicates blood in lateral ventricle. [Image used with permission of James Anderson, MD, Department of Radiology, Oregon Health & Science University.] Tintinalli_Sec14_p1101-1186.indd 1115 8/2/19 12:08 PM

rrhage with associated ventricular hemor rhage. Top arrow indicates blood in interhemispheric fissure. Bottom arrow indicates blood in lateral ventricle. [Image used with permission of James Anderson, MD, Department of Radiology, Oregon Health & Science University.] Tintinalli_Sec14_p1101-1186.indd 1115 8/2/19 12:08 PM 1116 SECTION 14: Neurology in the final tube was associated with an increase in the odds of sub arachnoid hemorrhage by a factor of 6. 32 Unfortunately, the literature remains unclear on the precise threshold number of RBCs needed in the CSF to be considered diagnostic of subarachnoid hemorrhage . In general, normal findings on head CT, the absence of xanthochro mia, and zero or few RBCs (<5 × 10 6 RBCs/L) in the CSF help reliably exclude subarachnoid hemorrhage. 33 A normal head CT result with a positive finding of xanthochromia or elevated RBC count in tube 4 should be considered diagnostic of subarachnoid hemorrhage.  SUBARACHNOID HEMORRHAGE GRADING SCALES Many different subarachnoid hemorrhage grading scales exist. Those most widely used include the Hunt and Hess scale and the World Federation of Neurosurgical Societies scale ( Table 166-3). A higher grade on either scale indicates a higher likelihood of poor outcome. TREATMENT Medical management of the subarachnoid hemorrhage patient in the ED should occur in a monitored critical care area and should target the prevention of complications. Reassess the Glasgow Coma Scale and pupil lary responses regularly because a decrease of 1 Glasgow Coma Scale point may indicate the onset of complications. 2 Intracerebral and extracerebral complications of subarachnoid hemorrhage include rebleeding, vasospasm, cerebral infarction, cerebral edema, hydrocephalus, intra cranial hypertension, fluid status and electrolyte abnormalities, respiratory failure, myocardial dysfunction, thromboembolism, and sepsis. The risk of rebleeding is greatest in the first 2 to 12 hours and can be reduced by adequate blood pressure control. Control blood pressure with a titratable agent to balance the risk of stroke, hypertension-related rebleeding, and maintenance of cerebral perfusion pressure. While target pressures have not yet been established, a decrease in systolic blood pressure to a range of 120 to 160 mm Hg is reasonable. 16 Because blood pressure may fluctuate through the course of the disease, a titratable IV antihypertensive is preferred. Labetalol and nicardipine are often used, with neither demonstrating clear superiority. Avoid nitroprusside and nitroglycerin because they increase cerebral blood volume and intracranial pressure. 35-37 There is debate regarding the use of antifibrinolytics to prevent rebleeding after subarachnoid hemorrhage, with weak evidence supporting short- but not long-term use in the first 7 days. 38 Generally, antifibrinolytics are not used because there is a risk of increased cerebral ischemia, as well as other dangerous complications. 38 However, in scenarios where there is an unavoidable delay in aneurysm obliteration, significant risk of rebleeding, and no major contraindications, initiation of tranexamic acid or aminocaproic acid in the ED is reasonable to reduce the risk of early aneurysm rebleeding, but should be done only in consultation with the accepting neurosurgeon given high complication rates. 16 Pain medications and antiemetics are also critical adjuncts in maintaining the alert patient’s comfort and blood pressure. Vasospasm is most common 2 days to 3 weeks after subarachnoid hemorrhage. A modest protective benefit is seen with administration of nimodipine, 60 milligrams PO every 4 hours, and this therapy should be initiated within 96 hours of symptom onset unless contraindicated due to allergy, nonfunctioning GI tract, or hepatic disease.

is most common 2 days to 3 weeks after subarachnoid hemorrhage. A modest protective benefit is seen with administration of nimodipine, 60 milligrams PO every 4 hours, and this therapy should be initiated within 96 hours of symptom onset unless contraindicated due to allergy, nonfunctioning GI tract, or hepatic disease. Clinical trials of other novel treatments, including statins, magnesium, and endothelin receptor antagonist, have not demonstrated significant reductions in mortality. 39-43 Delayed cerebral ischemia is associated with hypothermia, hyperthermia, and hyperglycemia. Prevent these conditions with the appropriate use of warming or cooling blankets, antipyretics, or insulin as indicated. Approximately 5% to 20% of patients with subarachnoid hemor rhage have at least one seizure. Consideration of seizure prophylaxis is currently supported by several clinical guidelines; however, this topic remains controversial and should be determined in conjunction with the intensivist or neurosurgeon who will manage the patient. DISPOSITION AND FOLLOW-UP Admit all patients diagnosed with subarachnoid hemorrhage to an intensive care unit in consultation with a neurosurgeon. In patients with normal findings on head CT and CSF analysis within 2 weeks of occur rence of initial headache symptoms, another explanation for symptoms should be pursued; these patients may be safe for discharge from the ED. 2,45 Consider consultation with a neurosurgeon for patients who present >2 weeks after the sudden onset of a severe headache causing FIGURE 166-2. Scattered subarachnoid hemorrhages ( arrows). [Image used with permission of James Anderson, MD, Department of Radiology, Oregon Health & Science University.] TABLE 166–3 Grading Scales for Subarachnoid Hemorrhage Grade Hunt and Hess Scale World Federation of Neurosurgical Societies Scale 1 Mild headache, normal mental status, no cranial nerve or motor findings GCS of 15, no motor deficits 2 Severe headache, normal mental status, may have cranial nerve deficit GCS of 13 or 14, no motor deficits 3 Somnolent, confused, may have cranial nerve or mild motor deficit GCS of 13 or 14, with motor deficits 4 Stupor, moderate to severe motor deficit, may have intermittent reflex posturing GCS of 7–12, with or without motor deficits 5 Coma, reflex posturing or flaccid GCS of 3–6, with or without motor deficits Abbreviation: GCS = Glasgow Coma Scale score. Source: Reproduced with permission from Hemphill JC: Neurologic critical care, in Fauci AS, Braunwald E, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, 17th ed. © McGraw-Hill, Inc., New York, 2008. Tintinalli_Sec14_p1101-1186.indd 1116 8/2/19 12:08 PM

s Abbreviation: GCS = Glasgow Coma Scale score. Source: Reproduced with permission from Hemphill JC: Neurologic critical care, in Fauci AS, Braunwald E, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, 17th ed. © McGraw-Hill, Inc., New York, 2008. Tintinalli_Sec14_p1101-1186.indd 1116 8/2/19 12:08 PM CHAPTER 166: Spontaneous Subarachnoid and Intracerebral Hemorrhage 1117 suspicion for subarachnoid hemorrhage if the initial workup yields normal findings.2  INTRACEREBRAL HEMORRHAGE EPIDEMIOLOGY Spontaneous intracerebral hemorrhage causes 8% to 11% of all acute strokes and is twice as common as subarachnoid hemorrhage. Like subarachnoid hemorrhage, intracerebral hemorrhage carries a high morbidity and mortality. Seven-day mortality is approximately 30%, 1-year mortality about 55%, and 10-year mortality approximately 80%. Among those who survive, only one in five will be functionally independent at 1 year. Intracerebral hemorrhage occurs greater than two times more frequently in blacks than in whites, which may be related to the higher prevalence of hypertension in blacks. 47 Additionally, intracerebral hemorrhage occurs in approximately 3% to 9% of patients treated with tissue plasminogen activator for acute ischemic stroke. The effect on intracerebral hemorrhage of both novel oral anticoagulants and vitamin K antagonists such as warfarin when used for atrial fibrillation to prevent ischemic stroke has been at the center of much debate and research. Overall, poorer outcomes have been observed in patients taking anticoagulants, whether novel oral anticoagulants or vitamin K antagonists, who develop intracerebral hemorrhage. 43,48 Importantly, novel oral anticoagulants are associated with reduced risk of intracerebral hemorrhage when compared to warfarin when used for stroke prevention in atrial fibrillation. 49 Anticoagulation with warfarin is a significant risk factor for intracerebral hemorrhage, with an annual intracerebral hemorrhage incidence of 0.3% to 0.6% in those taking the drug, and warfarin plays a role in 6% to 16% of all cases of intracerebral hemorrhage. Among patients taking warfarin, the risk of intracerebral hemorrhage nearly doubles for each 0.5 increase in international nor malized ratio above 4.5. When comparing novel oral anticoagulant–associated intracerebral hemorrhage with vitamin K antagonist–associated intracerebral hem orrhage, more research is needed. One pooled analysis reports that intracerebral hemorrhage volume, 90-day mortality, and functional outcomes are similar following both novel oral anticoagulant– and vitamin K antagonist–associated intracerebral hemorrhage, 50 whereas another prospective review and meta-analysis demonstrated that novel oral anticoagulant–associated intracerebral hemorrhage is associated with smaller baseline hematoma volume and lesser neurologic deficit at time of hospital admission when compared to vitamin K antagonist–associated intracerebral hemorrhage. 51 As more patients are being transitioned to novel oral anticoagulants, one study demonstrated that of patients who sustain intracerebral hemorrhage, in-hospital mortality is lower for those on novel oral anticoagulants as compared with those on vitamin K antagonists. 52,53 PATHOPHYSIOLOGY Risk factors for intracerebral hemorrhage include long-standing hyper tension, arteriovenous malformations, arterial aneurysm, anticoagulant therapy, use of sympathomimetic drugs (particularly cocaine and phenylpropanolamine), intracranial tumors, and amyloid angiopathy in the elderly. Current smoking and increased frequency of smoking also raise the risk of intracerebral hemorrhage, but the etiology of this increased risk is not as well defined as in ischemic stroke.

e of sympathomimetic drugs (particularly cocaine and phenylpropanolamine), intracranial tumors, and amyloid angiopathy in the elderly. Current smoking and increased frequency of smoking also raise the risk of intracerebral hemorrhage, but the etiology of this increased risk is not as well defined as in ischemic stroke. CLINICAL FEATURES Intracerebral hemorrhage may be clinically indistinguishable from cerebral infarction, subarachnoid hemorrhage, and ischemic stroke. In intracerebral hemorrhage, headache, nausea, and vomiting often precede the neurologic deficit, and in contrast to subarachnoid hemorrhage, the headache onset is usually more insidious. In hypertensive intracerebral hemorrhage, bleeding is usually localized to the putamen, thalamus, FIGURE 166–3. Large right-sided parietal intraparenchymal hemorrhage ( arrow). [Image used with permission of James Anderson, MD, Department of Radiology, Oregon Health & Science University.] pons, or cerebellum (in decreasing order of frequency), and clinical examination findings may be relatable to those areas. Cerebellar hemorrhage is commonly associated with dizziness, vomiting, marked truncal ataxia, gaze palsies, and depressed level of consciousness. Patients with cerebellar hemorrhage are more likely to have rapidly progressive symptoms and may require more aggressive intervention than patients with other forms of intracerebral hemorrhage. DIAGNOSIS AND IMAGING The differential diagnosis of intracerebral hemorrhage is similar to that of subarachnoid hemorrhage. The history, rapidity of progression of symptoms, and other clinical features may suggest that intracerebral hemorrhage is more likely than subarachnoid hemorrhage or ischemic stroke, but these features are not adequate alone to make a clinical diagnosis. CT and MRI each have areas of superiority in evaluating a patient for intracerebral hemorrhage. CT is optimal for demonstrating hemorrhage extension into the ventricles, whereas MRI is superior for demonstrating underlying structural lesions. Either modality is considered acceptable as the initial study for diagnosing intracerebral hemorrhage. Widespread availability of CT and its short scan time make a noncon trast CT the initial study of choice in most EDs ( Figure 166-3). The addition of contrast may allow identification of masses or aneurysms. Cerebral angiography may be useful in selected patients in stable condition who do not require urgent surgery, particularly those in whom no obvious cause of bleeding is identified and those younger than 45 years of age without hypertension. Tintinalli_Sec14_p1101-1186.indd 1117 8/2/19 12:08 PM

of masses or aneurysms. Cerebral angiography may be useful in selected patients in stable condition who do not require urgent surgery, particularly those in whom no obvious cause of bleeding is identified and those younger than 45 years of age without hypertension. Tintinalli_Sec14_p1101-1186.indd 1117 8/2/19 12:08 PM 1118 SECTION 14: Neurology TREATMENT Treat patients with intracerebral hemorrhage in a monitored critical care area. Patients with cerebellar hemorrhage are at particularly high risk of rapid deterioration and may require rapid intervention for surgical evacuation of hemorrhage. 56,57 Maintain close attention to the patient’s airway and neurologic status. Reduce hyperthermia with antipyret ics, administer antiepileptic medications if seizures occur, aggressively manage hypo- or hyperglycemia (>160 milligrams/dL or 8.9 mmol/L), manage blood pressure, and reverse coagulopathy (if present). Manage elevated intracranial pressure by raising the head of the bed 30 degrees and providing appropriate analgesia and sedation. If more aggressive reduction of intracranial pressure is required—such as administration of osmotic diuretics or intubation with neuromuscular blockade and mild hyperventilation—invasive intracranial pressure monitoring is generally indicated. Corticosteroids should not be given for treatment of elevated ICP in intracerebral hemorrhage. Current guidelines for blood pressure management are listed in Table 166-4. 58 Importantly, the Antihypertensive Treatment of Acute Cerebral Hemorrhage II study demonstrated treatment of participants with intracerebral hemorrhage to achieve a target systolic blood pressure of 110 to 139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg.  REVERSE COAGULOPATHY Given the complexity and variety of antiplatelet and anticoagula tion agents in current use, institutional protocols should be available with clear algorithms listing the indications for, and dosing of, reversal agents (Table 166-5). If the coagulopathy is related to heparin use, administer protamine at approximately 1 milligram per 100 units of heparin, adjusting based on the time since the heparin was last given. For patients taking warfarin, provide reversal no matter what the value of the international normalized ratio. For further discussion, see Chapter 239, “Thrombotics and Antithrombotics. ” Several options exist for reversing warfarin-induced coagulopathy: vitamin K, fresh frozen plasma, recombinant factor VIIa, and prothrombin complex concentrates. Vitamin K, 5 to 10 milligrams IV , can fully reverse war farin-induced anticoagulation, but the full effect takes 12 to 24 hours to achieve, during which time the hematoma may continue to expand. 60 Fresh frozen plasma has a faster onset, but contains variable amounts of clotting factors, and the dose of 15 mL/kg requires a large volume infusion that many patients cannot tolerate. Fresh frozen plasma can be available for rapid administration as universal donor (AB+) without the need for type and cross-match . One common clinical issue has centered on the advisability of platelet transfusion after spontaneous primary intracerebral hemorrhage in patients who are taking antiplatelet therapy. A multicenter, randomized controlled trial found that administering platelets to this subset of patients who sustained a spontaneous intracerebral hemorrhage resulted in higher rates of mortality and serious adverse events compared to a group who received standard care. As a result, perform standard care without platelet transfusion for patients who are taking antiplatelet therapy.

ing platelets to this subset of patients who sustained a spontaneous intracerebral hemorrhage resulted in higher rates of mortality and serious adverse events compared to a group who received standard care. As a result, perform standard care without platelet transfusion for patients who are taking antiplatelet therapy. Recombinant factor VIIa does not improve survival or functional outcome after intracerebral hemorrhage.62 Prothrombin complex concentrates are effective and rapidly reverse oral anticoagulants; however, morbidity and mortality remain high even when the coagulopathy is reversed. 63 Manage intracerebral hemorrhage related to fibrinolytic therapy with standard intracerebral hemorrhage treatment along with platelet and cryoprecipitate infusions, although little evidence exists to guide therapy in these cases. REFERENCES The complete reference list is available online at www.TintinalliEM.com. TABLE 166-4 Suggested Guidelines for Treating Elevated Blood Pressure in Spontaneous Intracranial Hemorrhage58 Clinical Circumstances Management SBP >220 mm Hg Consider aggressive reduction of blood pressure with continuous IV infusion. SBP 150–220 mm Hg Acute lowering of SBP to 140 mm Hg is safe and can be effective for improving functional outcome. Abbreviation: SBP = systolic blood pressure. TABLE 166-5 Reversal of Anticoagulation for Intracerebral Hemorrhage Anticoagulant Reversal Agent Comment Warfarin Vitamin K 5–10 milligrams IV Onset of action of IV vitamin K is 2 h, with maximal effect at 6–24 h. PCC and IV vitamin K act synergistically in INR reduction. Fresh frozen plasma 2 units IV Full dose 15 mL/kg limited by volume. Prothrombin complex concentrate (PCC) 50 IU/kg IV Dose-related risk of thromboembolism; available as 3-factor (II, IX, X) and 4-factor (II, VII, IX, X) PCC; use what is available in your institution. Onset of action of PCC is about 30 min with a half-life of 4–6 h. Aspirin and adenosine diphosphate receptor agonists Obtain consultation if available when considering platelet infusion CAUTION: Platelet reversal may cause coronary or arterial thrombosis and worsen outcome. Unfractionated heparin (UFH) 1 milligram protamine/100 units of UFH; maximum dose, 50 milligrams; calculate last 3 h of heparin dose to determine protamine dose because heparin has short half-life Infusion rate ≤5 milligrams/min; risk of hypersensitivity in patients with fish allergy or prior protamine exposure: premedicate with hydrocortisone 500 milligrams IV and diphenhydramine 50 milligrams IV. Low-molecular-weight heparin (LMWH) If last dose within 8 h, give 1 milligram protamine/1 milligram LMWH; maximum dose, 50 milligrams See above protamine cautions. Infusion rate ≤5 milligrams/min; higher infusion rates can cause hypotension or bradycardia. If last dose 8–12 h ago, give 0.5 milligram protamine/1 milligram LMWH

ecular-weight heparin (LMWH) If last dose within 8 h, give 1 milligram protamine/1 milligram LMWH; maximum dose, 50 milligrams See above protamine cautions. Infusion rate ≤5 milligrams/min; higher infusion rates can cause hypotension or bradycardia. If last dose 8–12 h ago, give 0.5 milligram protamine/1 milligram LMWH If last dose ≥12 h ago, do not give protamine Direct thrombin inhibitor or factor Xa inhibitors Idarucizumab 5 grams IV to reverse dabigatran Tintinalli_Sec14_p1101-1186.indd 1118 8/2/19 12:08 PM