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Hospital usage of early do-not-resuscitate orders and outcome after intracerebral hemorrhage. Stroke 2004; 35:1130. 116. Zahuranec DB, Brown DL, Lisabeth LD, et al. Early care limitations independently predict mortality after intracerebral hemorrhage. Neurology 2007; 68:1651. 117. Creutzfeldt CJ, Becker KJ, Weinstein JR, et al. Do-not-attempt-resuscitation orders and prognostic models for intraparenchymal hemorrhage. Crit Care Med 2011; 39:158. 118. Parry-Jones AR, Sammut-Powell C, Paroutoglou K, et al. An Intracerebral Hemorrhage Care Bundle Is Associated with Lower Case Fatality. Ann Neurol 2019; 86:495. 119. Cucchiara B, Messe S, Sansing L, et al. Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke 2008; 39:2993. https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 37/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate 120. Falcone GJ, Biffi A, Brouwers HB, et al. Predictors of hematoma volume in deep and lobar supratentorial intracerebral hemorrhage. JAMA Neurol 2013; 70:988. 121. Flaherty ML, Tao H, Haverbusch M, et al. Warfarin use leads to larger intracerebral hematomas. Neurology 2008; 71:1084. 122. Saloheimo P, Ahonen M, Juvela S, et al. Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death. Stroke 2006; 37:129. 123. Rosand J, Eckman MH, Knudsen KA, et al. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004; 164:880. 124. Xian Y, Zhang S, Inohara T, et al. Clinical Characteristics and Outcomes Associated With Oral Anticoagulant Use Among Patients Hospitalized With Intracerebral Hemorrhage. JAMA Netw Open 2021; 4:e2037438. 125. Dowlatshahi D, Butcher KS, Asdaghi N, et al. Poor prognosis in warfarin-associated intracranial hemorrhage despite anticoagulation reversal. Stroke 2012; 43:1812. 126. Wilson D, Charidimou A, Shakeshaft C, et al. Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type. Neurology 2016; 86:360. 127. Takahashi H, Jimbo Y, Takano H, et al. Intracerebral Hematoma Occurring During Warfarin Versus Non-Vitamin K Antagonist Oral Anticoagulant Therapy. Am J Cardiol 2016; 118:222. 128. Wilson D, Seiffge DJ, Traenka C, et al. Outcome of intracerebral hemorrhage associated with different oral anticoagulants. Neurology 2017; 88:1693. 129. Gerner ST, Kuramatsu JB, Sembill JA, et al. Characteristics in Non-Vitamin K Antagonist Oral Anticoagulant-Related Intracerebral Hemorrhage. Stroke 2019; 50:1392. 130. Toyoda K, Okada Y, Minematsu K, et al. Antiplatelet therapy contributes to acute deterioration of intracerebral hemorrhage. Neurology 2005; 65:1000. 131. Naidech AM, Bernstein RA, Levasseur K, et al. Platelet activity and outcome after intracerebral hemorrhage. Ann Neurol 2009; 65:352. 132. Naidech AM, Jovanovic B, Liebling S, et al. Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerebral hemorrhage. Stroke 2009; 40:2398. 133. Foerch C, Sitzer M, Steinmetz H, Neumann-Haefelin T. Pretreatment with antiplatelet agents is not independently associated with unfavorable outcome in intracerebral hemorrhage. Stroke 2006; 37:2165. 134. Nilsson OG, Lindgren A, Brandt L, S veland H. Prediction of death in patients with primary intracerebral hemorrhage: a prospective study of a defined population. J Neurosurg 2002; 97:531. https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 38/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate 135. Flibotte JJ, Hagan N, O'Donnell J, et al. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology 2004; 63:1059. 136. Sansing LH, Messe SR, Cucchiara BL, et al. Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH. Neurology 2009; 72:1397. 137. Thompson BB, B jot Y, Caso V, et al. Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review. Neurology 2010; 75:1333. 138. Apostolaki-Hansson T, Ullberg T, Pihlsg rd M, et al. Prognosis of Intracerebral Hemorrhage Related to Antithrombotic Use: An Observational Study From the Swedish Stroke Register (Riksstroke). Stroke 2021; 52:966. 139. Spr gel MI, Kuramatsu JB, Gerner ST, et al. Antiplatelet Therapy in Primary Spontaneous and Oral Anticoagulation-Associated Intracerebral Hemorrhage. Stroke 2018; 49:2621. 140. Passero S, Ciacci G, Ulivelli M. The influence of diabetes and hyperglycemia on clinical course after intracerebral hemorrhage. Neurology 2003; 61:1351. 141. Fogelholm R, Murros K, Rissanen A, Avikainen S. Admission blood glucose and short term survival in primary intracerebral haemorrhage: a population based study. J Neurol Neurosurg Psychiatry 2005; 76:349. 142. Appelboom G, Piazza MA, Hwang BY, et al. Severity of intraventricular extension correlates with level of admission glucose after intracerebral hemorrhage. Stroke 2011; 42:1883. 143. B jot Y, Aboa-Eboul C, Hervieu M, et al. The deleterious effect of admission hyperglycemia on survival and functional outcome in patients with intracerebral hemorrhage. Stroke 2012; 43:243. 144. Stead LG, Jain A, Bellolio MF, et al. Emergency Department hyperglycemia as a predictor of early mortality and worse functional outcome after intracerebral hemorrhage. Neurocrit Care 2010; 13:67. 145. Saxena A, Anderson CS, Wang X, et al. Prognostic Significance of Hyperglycemia in Acute Intracerebral Hemorrhage: The INTERACT2 Study. Stroke 2016; 47:682. 146. Rodriguez-Luna D, Rubiera M, Ribo M, et al. Serum low-density lipoprotein cholesterol level predicts hematoma growth and clinical outcome after acute intracerebral hemorrhage. Stroke 2011; 42:2447. 147. Di Napoli M, Godoy DA, Campi V, et al. C-reactive protein level measurement improves mortality prediction when added to the spontaneous intracerebral hemorrhage score. Stroke 2011; 42:1230. 148. Jordan LC, Kleinman JT, Hillis AE. Intracerebral hemorrhage volume predicts poor neurologic outcome in children. Stroke 2009; 40:1666. https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 39/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate 149. Hemphill JC 3rd, Bonovich DC, Besmertis L, et al. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 2001; 32:891. 150. Portenoy RK, Lipton RB, Berger AR, et al. Intracerebral haemorrhage: a model for the prediction of outcome. J Neurol Neurosurg Psychiatry 1987; 50:976. 151. Young WB, Lee KP, Pessin MS, et al. Prognostic significance of ventricular blood in supratentorial hemorrhage: a volumetric study. Neurology 1990; 40:616. 152. Lisk DR, Pasteur W, Rhoades H, et al. Early presentation of hemispheric intracerebral hemorrhage: prediction of outcome and guidelines for treatment allocation. Neurology 1994; 44:133. 153. Tuhrim S, Horowitz DR, Sacher M, Godbold JH. Volume of ventricular blood is an important determinant of outcome in supratentorial intracerebral hemorrhage. Crit Care Med 1999; 27:617. 154. Hallevi H, Albright KC, Aronowski J, et al. Intraventricular hemorrhage: Anatomic relationships and clinical implications. Neurology 2008; 70:848. 155. Staykov D, Volbers B, Wagner I, et al. Prognostic significance of third ventricle blood volume in intracerebral haemorrhage with severe ventricular involvement. J Neurol Neurosurg Psychiatry 2011; 82:1260. 156. Maas MB, Nemeth AJ, Rosenberg NF, et al. Subarachnoid extension of primary intracerebral hemorrhage is associated with poor outcomes. Stroke 2013; 44:653. 157. Morotti A, Arba F, Boulouis G, Charidimou A. Noncontrast CT markers of intracerebral hemorrhage expansion and poor outcome: A meta-analysis. Neurology 2020; 95:632. 158. Dowlatshahi D, Demchuk AM, Flaherty ML, et al. Defining hematoma expansion in intracerebral hemorrhage: relationship with patient outcomes. Neurology 2011; 76:1238. 159. Lee SH, Kim BJ, Ryu WS, et al. White matter lesions and poor outcome after intracerebral hemorrhage: a nationwide cohort study. Neurology 2010; 74:1502. 160. Caprio FZ, Maas MB, Rosenberg NF, et al. Leukoaraiosis on magnetic resonance imaging correlates with worse outcomes after spontaneous intracerebral hemorrhage. Stroke 2013; 44:642. 161. Uniken Venema SM, Marini S, Lena UK, et al. Impact of Cerebral Small Vessel Disease on Functional Recovery After Intracerebral Hemorrhage. Stroke 2019; 50:2722. 162. Menon RS, Burgess RE, Wing JJ, et al. Predictors of highly prevalent brain ischemia in intracerebral hemorrhage. Ann Neurol 2012; 71:199. 163. Garg RK, Liebling SM, Maas MB, et al. Blood pressure reduction, decreased diffusion on MRI, and outcomes after intracerebral hemorrhage. Stroke 2012; 43:67. https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 40/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate 164. Cheung RT, Zou LY. Use of the original, modified, or new intracerebral hemorrhage score to predict mortality and morbidity after intracerebral hemorrhage. Stroke 2003; 34:1717. 165. Godoy DA, Pi ero G, Di Napoli M. Predicting mortality in spontaneous intracerebral hemorrhage: can modification to original score improve the prediction? Stroke 2006; 37:1038. 166. Hemphill JC 3rd, Farrant M, Neill TA Jr. Prospective validation of the ICH Score for 12-month functional outcome. Neurology 2009; 73:1088. 167. Rost NS, Smith EE, Chang Y, et al. Prediction of functional outcome in patients with primary intracerebral hemorrhage: the FUNC score. Stroke 2008; 39:2304. 168. Garrett JS, Zarghouni M, Layton KF, et al. Validation of clinical prediction scores in patients with primary intracerebral hemorrhage. Neurocrit Care 2013; 19:329. 169. Parry-Jones AR, Abid KA, Di Napoli M, et al. Accuracy and clinical usefulness of intracerebral hemorrhage grading scores: a direct comparison in a UK population. Stroke 2013; 44:1840. Topic 1084 Version 62.0 https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 41/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate GRAPHICS Acute spontaneous intracerebral hemorrhage: Rapid overview of emergency management Clinical features Stroke symptoms: sudden onset loss of function in speech, vision, movement, sensation, balance Features suggestive of ICH over ischemic stroke: progressive worsening of acute symptoms; severely elevated SBP (eg, >220 mmHg); patient taking anticoagulant Signs of elevated ICP (mass effect from ICH): Dilated pupil Progressive drowsiness Cushing triad (bradycardia, respiratory depression, hypertension) Evaluation Assess airway, breathing, circulation, and disability to initiate supportive care Determine GCS, neurologic deficits Obtain emergency imaging (eg, head CT or fast MRI) Initial laboratory evaluation: complete blood count, PT, PTT, INR, basic electrolytes, glucose, cardiac-specific troponin, pregnancy test in females of childbearing age Serial monitoring (hourly) for neurologic deterioration or signs of elevated ICP Treatment* Perform tracheal intubation for any patient unable to protect their airway or with rapidly deteriorating mental status or GCS 8 Obtain immediate neurosurgical consultation for imaging findings indicating need for emergency surgery: 3 Cerebellar ICH that is either 3 cm diameter or causing brainstem compression IVH with obstructive hydrocephalus and neurologic deterioration Hemispheric ICH with life-threatening brain compression or obstructive hydrocephalus Reverse anticoagulation (agent specific): Warfarin (4-factor PCC with IV vitamin K) https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 42/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Dabigatran (idaricizumab) Factor Xa inhibitors: apixaban, edoxaban, rivaroxaban (4-factor PCC or andexanet alfa) Unfractionated heparin (protamine sulfate) Low molecular weight heparin (andexanet alfa; protamine sulfate is an alternative) Manage hypertension: Immediate treatment to reduce SBP below 220 mmHg: nicardipine starting at 5 mg/hour IV; alternate: labetalol 20 mg IV bolus, may repeat every 10 minutes Subsequent, stepwise treatment, typically over first 1 to 2 hours, to reduce SBP to 140 to 160 mmHg; monitor for neurologic deterioration Manage elevated intracranial pressure: General preventive measures: Elevate head of bed >30 degrees Give mild sedation as needed for comfort for intubated patients (eg, midazolam) Give antipyretics for temperature >38 C (eg, acetaminophen [paracetamol] 325 to 650 mg orally or PR every 4 to 6 hours or 650 mg IV every 4 hours) Maintain neutral head positioning; avoid rotating the neck or placing IV lines or devices in or at the neck that may impede venous outflow Use isotonic solutions for volume resuscitation and maintenance fluids; maintain serum sodium >135 mEq/L Repeat imaging (eg, head CT) for neurologic deterioration or signs of elevated ICP: Obtain immediate neurosurgical consultation for surgical indications (refer to above) Give osmotic therapy via central venous catheter for clinical signs or imaging findings of elevated ICP: Hypertonic saline 23.4%: 15 to 30 mL IV bolus every 6 hours, or Mannitol: 0.25 to 1 g/kg IV bolus every 6 hours ICH: intracerebral hemorrhage; SBP: systolic blood pressure; ICP: intracranial pressure; GCS: Glasgow coma scale; CT: computed tomography; MRI: magnetic resonance imaging; PT: prothrombin time; PTT: partial thromboplastin time; INR: international normalized ratio; IVH: intraventricular hemorrhage; PCC: prothrombin complex concentrate; IV: intravenous; PR: per rectum. Treatment steps for the acute management of ICH may be performed in parallel if resources are available. https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 43/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Graphic 132288 Version 5.0 https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 44/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Emergency reversal of anticoagulation from warfarin for life-threatening hemorrhage in adults: Suggested approaches based upon available resources A. If 4-factor prothrombin complex concentrate (4F PCC) is available (preferred approach): 1. Give 4F PCC* 1500 to 2000 units IV over 10 minutes. Check INR 15 minutes after completion of the infusion. If INR is not 1.5, give additional 4F PCC (refer to topic or drug reference for details). 2. Give vitamin K 10 mg IV over 10 to 20 minutes. B. If 3-factor prothrombin complex concentrate (3F PCC) is available but 4F PCC is not available: 1. Give 3F PCC* 1500 to 2000 units IV over 10 minutes. Check INR 15 minutes after completion of the infusion. If INR is not 1.5, give additional 3F PCC (refer to topic or drug reference for details). 2. Give Factor VIIa 20 mcg/kg IV OR give FFP 2 units IV by rapid infusion. Factor VIIa may be preferred if volume overload is a concern. 3. Give vitamin K 10 mg IV over 10 to 20 minutes. C. If neither 3F PCC nor 4F PCC is available: 1. Give FFP 2 units IV by rapid infusion. Check INR 15 minutes after completion of infusion. If INR 1.5, administer 2 additional units of FFP IV rapid infusion. Repeat process until INR 1.5. May wish to administer loop diuretic between FFP infusions if volume overload is a concern. 2. Give vitamin K 10 mg IV over 10 to 20 minutes. These products and doses are for use in life-threatening bleeding only. Evidence of life-threatening bleeding and over-anticoagulation with a vitamin K antagonist (eg, warfarin) are required. Anaphylaxis and transfusion reactions can occur. It may be reasonable to thaw 4 units of FFP while awaiting the PT/INR. The transfusion service may substitute other plasma products for FFP (eg, Plasma Frozen Within 24 Hours After Phlebotomy [PF24]); these products are considered clinically interchangeable. PCC will reverse anticoagulation within minutes of administration; FFP administration can take hours due to the volume required; vitamin K effect takes 12 to 24 hours, but administration of vitamin K is needed to counteract the long half-life of warfarin. Subsequent monitoring of the PT/INR is needed to guide further therapy. Refer to topics on warfarin reversal in individual situations for further management. PCC: unactivated prothrombin complex concentrate; 4F PCC: PCC containing coagulation factors II, VII, IX, X, protein S and protein C; 3F PCC: PCC containing factors II, IX, and X and only trace factor VII; FFP: fresh frozen plasma; PT: prothrombin time; INR: international normalized ratio; FEIBA: factor eight inhibitor bypassing agent. Before use, check product label to confirm factor types (3 versus 4 factor) and concentration. Activated complexes and single-factor IX products (ie, FEIBA, AlphaNine, Mononine, Immunine, BeneFix) are NOT used for warfarin reversal. https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 45/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate PCC doses shown are those suggested for initial treatment of emergency conditions. Subsequent treatment is based on INR and patient weight if available. Refer to topic and Lexicomp drug reference included with UpToDate for INR-based dosing. Graphic 89478 Version 10.0 https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 46/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Direct oral anticoagulant reversal agents for life-threatening bleeding (imminent risk of death from bleeding) Reversal agent (all are given Anticoagulant intravenously) Dabigatran (Pradaxa; oral thrombin inhibitor) Idarucizumab (Praxbind). Dose: 5 grams* Oral factor Xa inhibitors: Andexanet alfa (AndexXa). Dosing for the initial bolus and subsequent infusion depend Apixaban (Eliquis) on the dose level of the factor Xa inhibitor and the interval since it was last taken. Edoxaban (Lixiana, Savaysa) Rivaroxaban (Xarelto) OR- 4-factor PCC (Kcentra, Beriplex P/N, Octaplex). Dosing can be done with a fixed dose of 2000 units OR a weight-based dose of 25 to 50 units per kg. Reversal agents carry a risk of life-threatening thrombosis and should only be used under the direction of a specialist with expertise in their use and/or in a patient at imminent risk of death from bleeding. In general, a single dose is given; dosing may be repeated in rare situations in which the oral anticoagulant persists for longer in the circulation, such as severe kidney dysfunction. Andexanet dosing is as follows: If the patient took rivaroxaban >10 mg, apixaban >5 mg, or dose unknown within the previous 8 hours: Andexanet 800 mg bolus at 30 mg/minute followed by 960 mg infusion at 8 mg/minute for up to 120 minutes. OR- If the patient took rivaroxaban 10 mg or apixaban 5 mg, or if 8 hours have elapsed since the last dose of a factor Xa inhibitor: Andexanet 400 mg bolus at 30 mg/minute followed by 480 mg infusion at 4 mg/minute for up to 120 minutes. Refer to UpToDate topics on treatment of bleeding in patients receiving a DOAC or perioperative management of patients receiving a DOAC for additional information on administration, risks, and alternative therapies. DOAC: direct oral anticoagulant; PCC: prothrombin complex concentrate; FEIBA: factor eight inhibitor bypassing activity. If idarucizumab is unavailable, an activated PCC (FEIBA, 50 to 80 units per kg intravenously) may be a reasonable alternative. Graphic 112299 Version 9.0 https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 47/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Parenteral drugs for treatment of hypertensive emergencies in adults* Onset of Duration of Dose Drug action action Adverse effects Role range (minutes) (minutes) Vasodilators Clevidipine Initially 1 to 2 mg/hour as 2 to 4 5 to 15 Atrial fibrillation, nausea, lipid Hypertensive emergencies IV infusion formulation contains including with rapid titration. potential allergens (eg, soy, egg) postoperative hypertension. Most patients respond to 4 to 6 mg/hour and are treated with maximum doses of 21 mg/hour or less. NOTE: Delivered in lipid emulsion. 1000 mL maximum per 24 hours (equivalent to 21 mg/hour) due to lipid load. Enalaprilat 1.25 to 5 mg 15 to 30 approximately Precipitous fall in Acute left every 6 hours IV 6 to >12 hours pressure in high- renin states; variable ventricular fail Due to slow on response, headache, dizziness and long durat of effect, rarely used. Avoid use in AM kidney function https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 48/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate impairment, or pregnancy. Fenoldopam Initially 0.1 5 to 10 30 to 60 Tachycardia, Most hyperten mcg/kg per minute as headache, nausea, flushing emergencies. Use caution or IV infusion titrated to a avoid with glaucoma or maximum of 1.6 mcg/kg increased intracranial per minute pressure. 1 to 4 hours IV Hydralazine 10 to 20 mg IV 10 to 20 IV Sudden precipitous drop in blood In general, hydralazine sh pressure, tachycardia, flushing, be avoided due its prolonged a headache, vomiting, aggravation of angina unpredictable hypotensive ef 10 to 20 mg 20 to 30 IM 4 to 6 hours IM (40 mg maximum per labeling) IM Labetalol and nicardipine are generally prefe choices for treatment of eclampsia. Nicardipine 5 to 15 mg/hour as IV infusion. 5 to 15 approximately 1.5 to 4 hours Tachycardia, headache, dizziness, nausea, flushing, local phlebitis, edema Most hyperten emergencies, including pregnancy indu Some patients may require up to 30 mg/hour. Avoid use in ac heart failure. Caution with coronary ische Nitroglycerin 5 to 100 2 to 5 5 to 10 Hypoxemia, Potential adjun (glyceryl trinitrate) mcg/minute as IV infusion tachycardia (reflex sympathetic other IV antihypertensiv activation), therapy in pati headache, vomiting, flushing, with coronary ischemia (ACS) methemoglobinemia, tolerance with acute pulmona edema. prolonged use Nitroprusside 0.25 to 10 0.5 to 1 1 to 10 Elevated intracranial Due to its toxic mcg/kg per minute as IV pressure, decreased cerebral blood flow, nitroprusside should genera infusion. reduced coronary avoided if pref https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 49/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate To minimize blood flow in CAD, agents are risk of cyanide and available. cyanide toxicity, thiocyanate toxicity, nausea, vomiting, Nitroprusside should be avoi in patients with infusion duration muscle spasm, flushing, sweating AMI, CAD, CVA, should be as short as elevated intracranial possible and generally not pressure, kidne function exceed 2 impairment, or hepatic mcg/kg per minute. Use impairment. of maximal dose (ie, 8 to 10 mcg/kg per minute) should not exceed 10 minutes. Patients who receive higher doses (ie, >500 mcg/kg at a rate exceeding 2 mcg/kg per minute) should receive sodium thiosulfate infusion to avoid cyanide toxicity. Adrenergic inhibitors Esmolol 500 mcg/kg is typical 1 to 2 10 to 30 Nausea, flushing, bronchospasm, first- Perioperative hypertension. loading dose degree heart block, Avoid use in ac decompensate given over 1 minute; then infusion-site pain; half-life prolonged in heart failure. initiate IV infusion at setting of anemia https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 50/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate 25 to 50 mcg/kg per minute; titrate incrementally up to maximum of 300 mcg/kg per minute. May consider repeating a loading dose (eg, 500 mcg/kg) prior to each up-titration step. Labetalol Initial bolus of 20 mg IV followed by 20 to 80 mg IV bolus 5 to 10 2 to 4 hours Nausea/vomiting, paresthesias (eg, scalp tingling), bronchospasm, dizziness, nausea, Most hyperten emergencies including myocardial ischemia, every 10 minutes (maximum 300 mg) heart block hypertensive encephalopath pregnancy, and postoperative hypertension. or Avoid use in ac decompensate heart failure. 0.5 to 2 mg/minute as IV loading infusion following an initial 20 mg Use cautiously obstructive or reactive airway IV bolus (maximum 300 mg) Metoprolol Initially 1.25 20 5 to 8 hours Refer to labetalol Myocardial to 5 mg IV followed by ischemia, perioperative 2.5 to 15 mg IV every 3 to hypertension. Avoid use in ac 6 hours decompensate heart failure. https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 51/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Phentolamine 5 to 15 mg IV bolus every 5 1 to 2 10 to 30 Tachycardia, flushing, headache, Alternative opt for catecholam to 15 minutes nausea/vomiting excess (eg, adrenergic cris secondary to pheochromocy or cocaine overdose). IV: intravenous injection; AMI: acute myocardial infarction; IM: intramuscular injection; ACS: acute coronary syndrome; CAD: coronary artery disease; CVA: cerebrovascular accident. The treatment of acute aortic syndromes (eg, acute aortic dissection, aortic intramural hematoma) requires specific medication management to minimize disease extension and is presented separately. Refer to UpToDate topics discussing acute aortic syndromes and acute aortic dissection. Hypotension may occur with all agents. IV short-acting agents for treatment of hypertensive emergency should be administered immediately by clinicians who are trained and experienced in their titration using continuous noninvasive electronic monitoring of blood pressure, heart rate, and cardiac rhythm. Patients should be admitted to an intensive care unit as rapidly as possible. A combination of IV agents is often selected depending upon the acute indication. Refer to appropriate UpToDate clinical topic for suggested combinations. Initial fenoldopam doses in range of 0.01 to 0.3 mcg/kg per minute have been described. References: 1. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Hypertension 2018; 71:e140-e144]. Hypertension 2018; 71:e13-e115. 2. Marik PE, Varon J. Hypertensive crises: Challenges and management. Chest 2007; 131:1949. 3. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42:1206. 4. Varon J. Treatment of acute severe hypertension: Current and newer agents. Drugs 2008; 68:283. Graphic 64066 Version 36.0 https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 52/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Management of intracranial pressure for patients with acute intracerebral hemorrhage* ICH: intracerebral hemorrhage; ICP: intracranial pressure. For patients with ICH without premorbid advanced directives specifying limitations of invasive care. Hemostatic and blood pressure issues should be addressed simultaneously. Refer to the UpToDate topic for additional details. Maintain midline head position, avoid internal jugular catheters, and avoid tight device securement (eg, device ties, endotracheal tube holder, or intravenous line dressings). Graphic 132294 Version 2.0 https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 53/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Richmond Agitation-Sedation Scale (RASS) Score Term Description +4 Combative Overtly combative or violent, immediate danger to staff +3 Very agitated Pulls on or removes tubes or catheters, aggressive behavior toward staff +2 Agitated Frequent nonpurposeful movement or patient-ventilator dyssynchrony +1 Restless Anxious or apprehensive but movements not aggressive or vigorous 0 Alert and calm 1 Drowsy Not fully alert, sustained (>10 seconds) awakening, eye contact to voice 2 Light sedation Briefly (<10 seconds) awakens with eye contact to voice 3 Moderate sedation Any movement (but no eye contact) to voice 4 Deep sedation No response to voice, any movement to physical stimulation 5 Unarousable No response to voice or physical stimulation Procedure 1. Observe patient. Is patient alert and calm (score 0)? 2. Does patient have behavior that is consistent with restlessness or agitation? Assign score +1 to +4 using the criteria listed above. 3. If patient is not alert, in a loud speaking voice state patient's name and direct patient to open eyes and look at speaker. Repeat once if necessary. Can prompt patient to continue looking at speaker. Patient has eye opening and eye contact, which is sustained for more than 10 seconds (score -1). Patient has eye opening and eye contact, but this is not sustained for 10 seconds (score -2). Patient has any movement in response to voice, excluding eye contact (score -3). 4. If patient does not respond to voice, physically stimulate patient by shaking shoulder and then rubbing sternum if there is no response. Patient has any movement to physical stimulation (score -4). Patient has no response to voice or physical stimulation (score -5). Reproduced with permission from: Sessler C, Gosnell M, Grap MJ, et al. The Richmond agitation-sedation scale. Validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002; 166:1338. Copyright 2002 American https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 54/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Thoracic Society. Graphic 57874 Version 2.0 https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 55/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Clinical progression of transtentorial herniation Headache Altered level of consciousness Dilation of ipsilateral pupil Cranial nerve III palsy Ptosis Loss of medial gaze Decerebrate posturing Hemiparesis Dilation of opposite pupil Alteration of respiration Bradycardia Hypertension Respiratory arrest Graphic 70683 Version 2.0 https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 56/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Glasgow Coma Scale (GCS) Score Eye opening Spontaneous 4 Response to verbal command 3 Response to pain 2 No eye opening 1 Best verbal response Oriented 5 Confused 4 Inappropriate words 3 Incomprehensible sounds 2 No verbal response 1 Best motor response Obeys commands 6 Localizing response to pain 5 Withdrawal response to pain 4 Flexion to pain 3 Extension to pain 2 No motor response 1 Total The GCS is scored between 3 and 15, 3 being the worst and 15 the best. It is composed of three parameters: best eye response (E), best verbal response (V), and best motor response (M). The components of the GCS should be recorded individually; for example, E2V3M4 results in a GCS score of 9. A score of 13 or higher correlates with mild brain injury, a score of 9 to 12 correlates with moderate injury, and a score of 8 or less represents severe brain injury. Graphic 81854 Version 9.0 https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 57/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Transtentorial herniation Data from: Plum F, Posner JB. The Diagnosis of Stupor and Coma III. FA Davis, Philadelphia 1995. p. 103. Graphic 76974 Version 5.0 https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 58/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Pharmacologic properties of antiseizure medications Enzyme or Metabolism and Protein binding Half-lif transporter clearance (%) adults (h induction/inhibition* 20 Brivaracetam Metabolized Inhibits epoxide 9 primarily by CYP- independent hydroxylase hydrolysis (60%) and CYP2C19 (30%) Dose adjustment is needed in hepatic impairment Cannabidiol Hepatic (primarily) and gut by CYP2C19, CYP3A4, UGT1A7, UGT1A9, and UGT2B7 to Inhibits BCRP/ABCG2, BSEP/ABCB11, CYP2C19 (moderate) >94 56 to 61 May increase serum concentration of clobazam and the active metabolite(s) of clobazam active metabolite 7- OH-CBD and then to inactive metabolite 7-COOH-CBD Dose adjustment is needed in moderate to severe hepatic impairment Carbamazepine >90% metabolized by CYPs 3A4 (major) Potent and broad- spectrum inducer of CYP, 75 25 to 65 (init enzyme-ind and 1A2/2C8 (minor) to active (epoxide) UGT-glucuronidation, and P-gp naive patien 8 to 22 (afte and inactive weeks due t induction) metabolites Dose adjustment is needed in severe renal impairment; use is not recommended in moderate or severe hepatic impairment Cenobamate Primarily May increase serum 60 50 to 60 hou metabolized by glucuronidation via concentrations of clobazam, phenobarbital, https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 59/79 7/5/23, 12:24 PM