Intracerebral hemorrhage management: Difference between revisions

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Created page with "__NOTOC__ {{Intracerebral hemorrhage}} {{CMG}}; {{AE}} {{SaraM}} ==Overview== ==Management== ==References== {{reflist|2}} Category:Neurology Category:Cardiology..."
 
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==Management==
==Management==
[[Anticoagulant]]s and antithrombotics, key in treating ischemic stroke, can make bleeding worse and cannot be used in intracerebral hemorrhage.  Patients are monitored and their blood pressure, blood sugar, and oxygenation are kept at optimum levels.
===Coagulation factor deficiency or platelet disorder treatments===
Patients with a known coagulation factor deficiency or platelet disorder:<ref name=Schulman> Schulman S, Bijsterveld NR. Anticoagulants and their reversal. Transfus Med Rev. 2007;21:37–48. doi: 10.1016/j.tmrv.2006.08.002.</ref><ref name=Andrews>Andrews CM, Jauch EC, Hemphill JC 3rd, Smith WS, Weingart SD. Emergency neurological life support: intracerebral hemorrhage. Neurocrit Care. 2012;17(suppl 1):S37–S46. doi: 10.1007/s12028-012-9757-2.</ref>
*Replacement of the appropriate factor or platelets
*Hematology consult 
patient undergoing an IV [[heparin]] infusion
*[[Protamine sulfate]] IV injection at a dose of 1 mg per 100 U of heparin (maximum dose 50 mg) with adjustment based on time elapsed since discontinuation of heparin infusion
Patients who are receiving [[low-molecular-weight heparin]] (reversal may be incomplete)
*[[Protamine sulfate]] IV injection at a dose of 1 mg per 100 U of heparin (maximum dose 50 mg)
===Vitamin K antagonists (VKAs)===
Rapid correction of the [[international normalized ratio|international normalized ratio (INR)]] is recommended.
*[[Fresh frozen plasma|Fresh frozen plasma (FFP)]], along with [[vitamin K]] (5 to 10 mg, usually given slowly via the IV route) has been the mainstay of treatment
Recently new treatments have emerged as potential therapies such as:<ref name=Holbrook> Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, Svensson PJ, Veenstra DL, Crowther M, Guyatt GH; American College of Chest Physicians. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e152S–e184S. doi: 10.1378/ chest.11-2295.</ref><ref name=Hanley>Hanley JP. Warfarin reversal. J Clin Pathol. 2004;57:1132–1139. doi: 10.1136/jcp.2003.008904.</ref>
*Prothrombin complex concentrates (PCCs) contains factors II, IX,  X, and VII. PCC does not require cross matching, can be reconstituted and administered rapidly in a small volume (20–40 mL) and Several studies have shown that PCCs rapidly normalize the INR (within minutes) in patients taking VKAs.
*Activated PCC FEIBA (factor VIII inhibitor bypassing activity)
*Recombinant [[activated factor VIIa]] (rFVIIa)
===New Anticoagulant Medication–Related ICH===
There are no randomized trials of reversing agents for newer [[anticoagulants]] among patients with ICH or other major bleeding complications.
Currently available agents in the United States (dabigatran, rivaroxaban, and apixaban) have relatively short half-lives ranging from 5 to 15 hours. Evaluation of the activated [[partial thromboplastin time]] and [[prothrombin time]] and consultation with a hematologist are reasonable to individualize care. Potential reversal strategies using FEIBA, other PCCs, or rFVIIa might be considered.
*Activated charcoal can be used if the most recent dose of dabigatran, apixaban, or rivaroxaban was taken within the previous couple of hours<ref name=Kaatz>Kaatz S, Kouides PA, Garcia DA, Spyropolous AC, Crowther M, Douketis JD, Chan AK, James A, Moll S, Ortel TL, Van Cott EM, Ansell J. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol. 2012;87 Suppl 1:S141–S145. doi: 10.1002/ ajh.23202.</ref>
*[[Fresh frozen plasma|FFP]] is of unclear utility, and [[vitamin K]] is not useful
*FEIBA or rFVIIa may be better for the [[direct thrombin inhibitor]] (dabigatran)
*PCCs may be better for the factor Xa inhibitors (rivaroxaban and apixaban)<ref name=dager>Dager WE, Gosselin RC, Roberts AJ. Reversing dabigatran in life-threat- ening bleeding occurring during cardiac ablation with factor eight inhibi- tor bypassing activity. Crit Care Med. 2013;41:e42–e46. doi: 10.1097/ CCM.0b013e31827caaa3.</ref><ref name=OH-JJ>Oh JJ, Akers WS, Lewis D, Ramaiah C, Flynn JD. Recombinant factor VIIa for refractory bleeding after cardiac surgery secondary to antico- agulation with the direct thrombin inhibitor lepirudin. Pharmacotherapy. 2006;26:569–577. doi: 10.1592/phco.26.4.576.</ref>
*Hemodialysis has been noted as an option for dabigatran, but less so for rivaroxaban or apixaban<ref name=Veshchev>Veshchev I, Elran H, Salame K. Recombinant coagulation factor VIIa for rapid preoperative correction of warfarin-related coagulopathy in patients with acute subdural hematoma. Med Sci Monit. 2002;8:CS98–CS100.</ref>
===Antiplatelet Medication–Related ICH===
Studies addressing the effect of prior antiplatelet agent use or platelet dysfunction on ICH growth and outcome have found conflicting results.<ref name=Sansing>Sansing LH, Messe SR, Cucchiara BL, Cohen SN, Lyden PD, Kasner SE; CHANT Investigators. Prior antiplatelet use does not affect hem- orrhage growth or outcome after ICH. Neurology. 2009;72:1397–1402. doi: 10.1212/01.wnl.0000342709.31341.88.</ref><ref name=Naidech> Naidech AM, Jovanovic B, Liebling S, Garg RK, Bassin SL, Bendok BR, Bernstein RA, Alberts MJ, Batjer HH. Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerebral hemorrhage. Stroke. 2009;40:2398–2401. doi: 10.1161/ STROKEAHA.109.550939.</ref><ref name=De-Gans>de Gans K, de Haan RJ, Majoie CB, Koopman MM, Brand A, Dijkgraaf MG, Vermeulen M, Roos YB; PATCH Investigators. PATCH: Platelet Transfusion in Cerebral Haemorrhage: study protocol for a multi- centre, randomised, controlled trial. BMC Neurol. 2010;10:19. doi: 10.1186/1471-2377-10-19.</ref><ref name=Naidech1>Naidech AM, Bernstein RA, Levasseur K, Bassin SL, Bendok BR, Batjer HH, Bleck TP, Alberts MJ. Platelet activity and outcome after intracerebral hemorrhage. Ann Neurol. 2009;65:352–356. doi: 10.1002/ ana.21618.</ref>
===Thromboprophylaxis in ICH Patients===
Patients with ICH have a high risk of thromboembolic disease.<ref name=Gregory>Gregory PC, Kuhlemeier KV. Prevalence of venous thromboembolism in acute hemorrhagic and thromboembolic stroke. Am J Phys Med Rehabil. 2003;82:364–369. doi: 10.1097/01.PHM.0000064725.62897.A5.</ref>
*intermittent pneumatic compression begun as early as the day of hospital admission reduced the occurrence of proximal DVT<ref name=CLOTS> Dennis M, Sandercock P, Reid J, Graham C, Forbes J, Murray G; CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial [published corrections appear in Lancet. 2013;382:506 and Lancet. 2013;382:1020]. Lancet. 2013;382:516–524. doi: 10.1016/S0140-6736(13)61050-8.</ref>
*ICH patients who develop DVT or PE may be considered for full systemic anticoagulation or placement of an inferior vena cava (IVC) filter<ref name=Kelly> Kelly J, Hunt BJ, Lewis RR, Rudd A. Anticoagulation or inferior vena cava filter placement for patients with primary intracerebral hemorrhage developing venous thromboembolism? Stroke. 2003;34:2999–3005. doi: 10.1161/01.STR.0000102561.86835.17.</ref>
===BP-Lowering Treatment===
*Overall, current evidence indicates that early intensive BP lowering is safe and feasible in patients with [[intracerebral hemorrhage|intracerebral hemorrhage (ICH)]] and that surviving patients show modestly better functional recovery, with a favorable trend seen toward a reduction in the conventional clinical end point of death and major disability.
*It is reasonable for [[intracerebral hemorrhage|intracerebral hemorrhage (ICH)]] patients to receive early treatment targeted to an SBP level <140 mmHg to improve their chances of achieving better functional recovery if they survive the condition.
*There are fewer data available pertaining to the safety and effectiveness of treatment in patients with very high BP (sustained SBP >220 mm Hg) on presentation, large and more severe ICH, and those requiring surgical decompression.
===Glucose management===
A randomized trial showing improved outcomes with tight glucose control (range, 80–110 mg/dL) using insulin infusions in mainly surgical critical care patients. However, h[[ypoglycemia]] should be avoided.<ref name=van-den-Berg>van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359–1367.</ref>
===Temperature managemen===
Although many studies provide a rationale for treatment of fever in [[intracerebral hemorrhage|intacerebaral hemorrhage (ICH)]] patients, maintenance of normothermia has not been clearly demonstrated as beneficial to outcome.<ref name=Middleton> Middleton S, McElduff P, Ward J, Grimshaw JM, Dale S, D’Este C, Drury P, Griffiths R, Cheung NW, Quinn C, Evans M, Cadilhac D, Levi C; QASC Trialists Group. Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial. Lancet. 2011;378:1699–1706. doi: 10.1016/S0140-6736(11)61485-2.</ref><ref name=Broessner>Broessner G, Beer R, Lackner P, Helbok R, Fischer M, Pfausler B, Rhorer J, Küppers-Tiedt L, Schneider D, Schmutzhard E. Prophylactic, endovascularly based, long-term normothermia in ICU patients with severe cerebrovascular disease: bicenter prospective, randomized trial. Stroke. 2009;40:e657–e665. doi: 10.1161/STROKEAHA.109.557652.</ref>
===Antiseizure drugs===
*[[Prophylactic]] anticonvulsant medication has not been demonstrated to be beneficial.
*Clinical seizures or [[electrographic|electrographic seizures]] in patients with a change in mental status should be treated with antisezure drugs.
*Continuous EEG monitoring should be considered in ICH patients with depressed mental status that is disproportionate to the degree of brain injury.
===ICP Monitoring and Treatment===
Because the usual causes of elevated [[ICP]] are [[hydrocephalus]] from [[IVH]] or mass effect from the [[hematoma]] (or surrounding edema), patients with small [[hematomas]] and limited IVH usually will not require treatment to lower ICP.
Patients with a GCS score of ≤8, those with clinical evidence of transtentorial herniation, or those with significant IVH or hydrocephalus might be consid- ered for ICP monitoring and treatment.
*Basic principles include:<ref name=wolfe> Wolfe TJ, Torbey MT. Management of intracranial pressure. Curr Neurol Neurosci Rep. 2009;9:477–485.</ref><ref name="pmid21242790">{{cite journal| author=Kamel H, Navi BB, Nakagawa K, Hemphill JC, Ko NU| title=Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials. | journal=Crit Care Med | year= 2011 | volume= 39 | issue= 3 | pages= 554-9 | pmid=21242790 | doi=10.1097/CCM.0b013e318206b9be | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21242790  }} </ref><ref name="pmid3574383">{{cite journal| author=Poungvarin N, Bhoopat W, Viriyavejakul A, Rodprasert P, Buranasiri P, Sukondhabhant S et al.| title=Effects of dexamethasone in primary supratentorial intracerebral hemorrhage. | journal=N Engl J Med | year= 1987 | volume= 316 | issue= 20 | pages= 1229-33 | pmid=3574383 | doi=10.1056/NEJM198705143162001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3574383  }} </ref>
**Elevation of the head of the bed to 30°
**Use of mild sedation,
**Avoidance of collar-endotracheal tube ties that might constrict cervical veins
**[[Mannitol]] or [[hypertonic saline]] (acute ICP elevations)
**CSF drainage should be considered (obstruction caused by [[hydrocephalus]] or a [[trapped ventricle]])
**Hematoma evacuation
**[[craniectomy|Decompressive craniectomy (DC)]]
**Salvage therapies
***[[Barbiturate]] coma
***Mild [[hypothermia]]
[[Corticosteroids]] should not be used, because they are not effective in ICH and increase complications
===Intraventricular hemorrhage===
*Clinical series have reported that intraventricular administration of [[fibrinolytic agents]], including [[urokinase]], [[streptokinase]], and recombinant [[tissue plasminogen activator|tissue-type plasminogen activator (rtPA)]], in IVH may reduce morbidity and mortality by accelerating blood clearance and clot lysis.<ref>Castaño Ávila S, Corral Lozano E, Vallejo De La Cueva A, Maynar Moliner J, Martín López A, Fonseca San Miguel F, Urturi Matos JA, Manzano Ramírez A. Intraventricular hemorrhage treated with intraven- tricular fibrinolysis: a 10-year experie</ref><ref>King NK, Lai JL, Tan LB, Lee KK, Pang BC, Ng I, Wang E. A ran- domized, placebo-controlled pilot study of patients with spontaneous intraventricular haemorrhage treated with intraventricular thrombolysis. J Clin Neurosci. 2012;19:961–964. doi: 10.1016/j.jocn.2011.09.030.</ref>
==2015 AHA/ASA Guidelines for the Management of Spontaneous Intracerebral Hemorrhage<ref name=ASA/AHA-ICH-Guid> 2015 AHA/ASA Guidelines for the Management of Spontaneous Intracerebral Hemorrhage http://stroke.ahajournals.org/content/early/2015/05/28/STR.0000000000000069 Accessed on November 10, 2016</ref>==
===Hemostasis and Coagulopathy, Antiplatelet Agents, and DVT Prophylaxis: Recommendations===
====Patients with a severe coagulation factor deficiency or severe thrombocytopenia====
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.'''Patients with a severe [[coagulation factor deficiency]] or severe [[thrombocytopenia]] should receive appropriate factor replacement therapy or platelets, respectivel ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
====Patients with ICH whose INR is elevated because of VKA====
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.'''Patients with ICH whose INR is elevated because of VKA should have their VKA withheld, receive therapy to replace vitamin K–dependent factors and correct the INR, and receive intravenous vitamin K ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (Harm)
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.'''rFVIIa does not replace all clotting factors, and although the INR may be lowered, clotting may not be restored in vivo; therefore, rFVIIa is not recommended for VKA reversal in ICH  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.'''PCCs may have fewer complications and correct the INR more rapidly than FFP and might be considered over FFP ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
====Patients with ICH who are taking dabigatran, rivaroxaban, or apixaban====
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.'''For patients with ICH who are taking dabigatran, rivaroxaban, or apixaban, treatment with FEIBA, other PCCs, or rFVIIa might be considered on an individual basis. Activated charcoal might be used if the most recent dose of dabigatran, apixaban, or riva- roxaban was taken <2 hours earlier. Hemodialysis might be considered for dabigatran ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
====Reverse heparin in patients with acute ICH====
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' [[Protamine sulfate]] may be considered to reverse [[heparin]] in patients with acute ICH ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
====Patients with a history of anti platelet and ICH====
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.'''The usefulness of platelet transfusions in ICH patients with a history of antiplatelet use is uncertain ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
====Hematoma expansion====
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (Harm)
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' Although rFVIIa can limit the extent of hematoma expansion in noncoagulopathic ICH patients, there is an increase in thromboembolic risk with rFVIIa and no clear clinical benefit in unselected patients. Thus, rFVIIa is not recommended ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|}
====prevention of venous thromboembolism====
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.'''Patients with ICH should have intermittent pneu- matic compression for prevention of venous throm- boembolism beginning the day of hospital admission ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|}
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (Harm)
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.'''Graduated compression stockings are not beneficial to reduce DVT or improve outcome  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|}
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.'''After documentation of cessation of bleeding, low- dose subcutaneous low-molecular-weight heparin or unfractionated heparin may be considered for pre- vention of venous thromboembolism in patients with lack of mobility after 1 to 4 days from onset ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
====ICH patients with symptom- atic DVT or PE ====
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.'''Systemic anticoagulation or IVC filter placement is probably indicated in ICH patients with symptom- atic DVT or PE ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' The decision between these 2 options should take into account several factors, including time from hem- orrhage onset, hematoma stability, cause of hemor- rhage, and overall patient condition ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
===BP-Lowering: Recommendations===
====ICH patients presenting with SBP between 150 and 220 mmHg====
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.'''For ICH patients presenting with SBP between 150 and 220 mmHg and without contraindication to acute BP treatment, acute lowering of SBP to 140 mm Hg is safe ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|}
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.'''For ICH patients presenting with SBP between 150 and 220 mmHg and without contraindication to acute BP treatment, acute lowering of SBP to 140 mm Hg ) can be effective for improving functional outcome ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
====ICH patients presenting with SBP >220 mmHg====
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' For ICH patients presenting with SBP >220 mm Hg, it may be reasonable to consider aggressive reduction of BP with a continuous intravenous infusion and frequent BP monitoring ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
===General Monitoring and Nursing Care: Recommendation===
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.'''Initial monitoring and management of ICH patients should take place in an intensive care unit or dedicated stroke unit with physician and nursing neuroscience acute care expertis ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
===Glucose Management: Recommendation===
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.'''Glucose should be monitored. Both [[hyperglycemia]] and [[hypoglycemi]]a should be avoided ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
===Temperature Management: Recommendation===
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.'''Treatment of fever after ICH may be reasonable ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
===Seizures and Antiseizure Drugs: Recommendations===
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.'''Clinical seizures should be treated with antiseizure drugs  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.'''Patients with a change in mental status who are found to have electrographic seizures on EEG should be treated with antiseizure drugs ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (Harm)
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.'''Prophylactic antiseizure medication is not recommended  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.'''Continuous EEG monitoring is probably indicated in ICH patients with depressed mental status that is out of proportion to the degree of brain injury ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
===Management of Medical Complications: Recommendations===
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.'''A formal screening procedure for [[dysphagia]] should be performed in all patients before the initiation of oral intake to reduce the risk of [[pneumonia]]  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Systematic screening for [[myocardial ischemia]] or infarction with [[electrocardiogram]] and [[cardiac enzyme testing]] after ICH is reasonable  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
===ICP Monitoring and Treatment: Recommendations===
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (Harm)
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.'''[[Corticosteroids]] should not be administered for treatment of elevated ICP in ICH  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.'''Ventricular drainage as treatment for [[hydrocephalus]] is reasonable, especially in patients with decreased level of consciousness  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Patients with a GCS score of ≤8, those with clinical evidence of [[transtentorial herniation]], or those with significant IVH or [[hydrocephalus]] might be considered for ICP monitoring and treatment. A CPP of 50 to 70 mm Hg may be reasonable to maintain depending on the status of cerebral autoregulation ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
===IVH: Recommendations===
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.'''Although intraventricular administration of rtPA in IVH appears to have a fairly low complication rate, the efficacy and safety of this treatment are uncertain ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.'''The efficacy of endoscopic treatment of IVH is uncertain ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}


==References==
==References==

Revision as of 03:15, 30 November 2016

Intracerebral hemorrhage Microchapters

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Management of ICH

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Overview

Management

Anticoagulants and antithrombotics, key in treating ischemic stroke, can make bleeding worse and cannot be used in intracerebral hemorrhage. Patients are monitored and their blood pressure, blood sugar, and oxygenation are kept at optimum levels.

Coagulation factor deficiency or platelet disorder treatments

Patients with a known coagulation factor deficiency or platelet disorder:[1][2]

  • Replacement of the appropriate factor or platelets
  • Hematology consult

patient undergoing an IV heparin infusion

  • Protamine sulfate IV injection at a dose of 1 mg per 100 U of heparin (maximum dose 50 mg) with adjustment based on time elapsed since discontinuation of heparin infusion

Patients who are receiving low-molecular-weight heparin (reversal may be incomplete)

  • Protamine sulfate IV injection at a dose of 1 mg per 100 U of heparin (maximum dose 50 mg)

Vitamin K antagonists (VKAs)

Rapid correction of the international normalized ratio (INR) is recommended.

Recently new treatments have emerged as potential therapies such as:[3][4]

  • Prothrombin complex concentrates (PCCs) contains factors II, IX, X, and VII. PCC does not require cross matching, can be reconstituted and administered rapidly in a small volume (20–40 mL) and Several studies have shown that PCCs rapidly normalize the INR (within minutes) in patients taking VKAs.
  • Activated PCC FEIBA (factor VIII inhibitor bypassing activity)
  • Recombinant activated factor VIIa (rFVIIa)

New Anticoagulant Medication–Related ICH

There are no randomized trials of reversing agents for newer anticoagulants among patients with ICH or other major bleeding complications. Currently available agents in the United States (dabigatran, rivaroxaban, and apixaban) have relatively short half-lives ranging from 5 to 15 hours. Evaluation of the activated partial thromboplastin time and prothrombin time and consultation with a hematologist are reasonable to individualize care. Potential reversal strategies using FEIBA, other PCCs, or rFVIIa might be considered.

  • Activated charcoal can be used if the most recent dose of dabigatran, apixaban, or rivaroxaban was taken within the previous couple of hours[5]
  • FFP is of unclear utility, and vitamin K is not useful
  • FEIBA or rFVIIa may be better for the direct thrombin inhibitor (dabigatran)
  • PCCs may be better for the factor Xa inhibitors (rivaroxaban and apixaban)[6][7]
  • Hemodialysis has been noted as an option for dabigatran, but less so for rivaroxaban or apixaban[8]

Antiplatelet Medication–Related ICH

Studies addressing the effect of prior antiplatelet agent use or platelet dysfunction on ICH growth and outcome have found conflicting results.[9][10][11][12]

Thromboprophylaxis in ICH Patients

Patients with ICH have a high risk of thromboembolic disease.[13]

  • intermittent pneumatic compression begun as early as the day of hospital admission reduced the occurrence of proximal DVT[14]
  • ICH patients who develop DVT or PE may be considered for full systemic anticoagulation or placement of an inferior vena cava (IVC) filter[15]

BP-Lowering Treatment

  • Overall, current evidence indicates that early intensive BP lowering is safe and feasible in patients with intracerebral hemorrhage (ICH) and that surviving patients show modestly better functional recovery, with a favorable trend seen toward a reduction in the conventional clinical end point of death and major disability.
  • It is reasonable for intracerebral hemorrhage (ICH) patients to receive early treatment targeted to an SBP level <140 mmHg to improve their chances of achieving better functional recovery if they survive the condition.
  • There are fewer data available pertaining to the safety and effectiveness of treatment in patients with very high BP (sustained SBP >220 mm Hg) on presentation, large and more severe ICH, and those requiring surgical decompression.

Glucose management

A randomized trial showing improved outcomes with tight glucose control (range, 80–110 mg/dL) using insulin infusions in mainly surgical critical care patients. However, hypoglycemia should be avoided.[16]

Temperature managemen

Although many studies provide a rationale for treatment of fever in intacerebaral hemorrhage (ICH) patients, maintenance of normothermia has not been clearly demonstrated as beneficial to outcome.[17][18]

Antiseizure drugs

  • Prophylactic anticonvulsant medication has not been demonstrated to be beneficial.
  • Clinical seizures or electrographic seizures in patients with a change in mental status should be treated with antisezure drugs.
  • Continuous EEG monitoring should be considered in ICH patients with depressed mental status that is disproportionate to the degree of brain injury.

ICP Monitoring and Treatment

Because the usual causes of elevated ICP are hydrocephalus from IVH or mass effect from the hematoma (or surrounding edema), patients with small hematomas and limited IVH usually will not require treatment to lower ICP.

Patients with a GCS score of ≤8, those with clinical evidence of transtentorial herniation, or those with significant IVH or hydrocephalus might be consid- ered for ICP monitoring and treatment.

Corticosteroids should not be used, because they are not effective in ICH and increase complications

Intraventricular hemorrhage

2015 AHA/ASA Guidelines for the Management of Spontaneous Intracerebral Hemorrhage[24]

Hemostasis and Coagulopathy, Antiplatelet Agents, and DVT Prophylaxis: Recommendations

Patients with a severe coagulation factor deficiency or severe thrombocytopenia

Class I
"1.Patients with a severe coagulation factor deficiency or severe thrombocytopenia should receive appropriate factor replacement therapy or platelets, respectivel (Level of Evidence: C)"

Patients with ICH whose INR is elevated because of VKA

Class I
"1.Patients with ICH whose INR is elevated because of VKA should have their VKA withheld, receive therapy to replace vitamin K–dependent factors and correct the INR, and receive intravenous vitamin K (Level of Evidence: C)"
Class III (Harm)
"1.rFVIIa does not replace all clotting factors, and although the INR may be lowered, clotting may not be restored in vivo; therefore, rFVIIa is not recommended for VKA reversal in ICH (Level of Evidence: C)"
Class IIb
"1.PCCs may have fewer complications and correct the INR more rapidly than FFP and might be considered over FFP (Level of Evidence: B)"

Patients with ICH who are taking dabigatran, rivaroxaban, or apixaban

Class IIb
"1.For patients with ICH who are taking dabigatran, rivaroxaban, or apixaban, treatment with FEIBA, other PCCs, or rFVIIa might be considered on an individual basis. Activated charcoal might be used if the most recent dose of dabigatran, apixaban, or riva- roxaban was taken <2 hours earlier. Hemodialysis might be considered for dabigatran (Level of Evidence: C)"

Reverse heparin in patients with acute ICH

Class IIb
"1. Protamine sulfate may be considered to reverse heparin in patients with acute ICH (Level of Evidence: C)"

Patients with a history of anti platelet and ICH

Class IIb
"1.The usefulness of platelet transfusions in ICH patients with a history of antiplatelet use is uncertain (Level of Evidence: C)"

Hematoma expansion

Class III (Harm)
"1. Although rFVIIa can limit the extent of hematoma expansion in noncoagulopathic ICH patients, there is an increase in thromboembolic risk with rFVIIa and no clear clinical benefit in unselected patients. Thus, rFVIIa is not recommended (Level of Evidence: A)"

prevention of venous thromboembolism

Class I
"1.Patients with ICH should have intermittent pneu- matic compression for prevention of venous throm- boembolism beginning the day of hospital admission (Level of Evidence: A)"
Class III (Harm)
"1.Graduated compression stockings are not beneficial to reduce DVT or improve outcome (Level of Evidence: A)"
Class IIb
"1.After documentation of cessation of bleeding, low- dose subcutaneous low-molecular-weight heparin or unfractionated heparin may be considered for pre- vention of venous thromboembolism in patients with lack of mobility after 1 to 4 days from onset (Level of Evidence: B)"

ICH patients with symptom- atic DVT or PE

Class IIa
"1.Systemic anticoagulation or IVC filter placement is probably indicated in ICH patients with symptom- atic DVT or PE (Level of Evidence: C)"
"2. The decision between these 2 options should take into account several factors, including time from hem- orrhage onset, hematoma stability, cause of hemor- rhage, and overall patient condition (Level of Evidence: C)"

BP-Lowering: Recommendations

ICH patients presenting with SBP between 150 and 220 mmHg

Class I
"1.For ICH patients presenting with SBP between 150 and 220 mmHg and without contraindication to acute BP treatment, acute lowering of SBP to 140 mm Hg is safe (Level of Evidence: A)"
Class IIa
"1.For ICH patients presenting with SBP between 150 and 220 mmHg and without contraindication to acute BP treatment, acute lowering of SBP to 140 mm Hg ) can be effective for improving functional outcome (Level of Evidence: C)"

ICH patients presenting with SBP >220 mmHg

Class IIb
"1. For ICH patients presenting with SBP >220 mm Hg, it may be reasonable to consider aggressive reduction of BP with a continuous intravenous infusion and frequent BP monitoring (Level of Evidence: C)"

General Monitoring and Nursing Care: Recommendation

Class I
"1.Initial monitoring and management of ICH patients should take place in an intensive care unit or dedicated stroke unit with physician and nursing neuroscience acute care expertis (Level of Evidence: B)"

Glucose Management: Recommendation

Class I
"1.Glucose should be monitored. Both hyperglycemia and hypoglycemia should be avoided (Level of Evidence: C)"

Temperature Management: Recommendation

Class IIb
"1.Treatment of fever after ICH may be reasonable (Level of Evidence: C)"

Seizures and Antiseizure Drugs: Recommendations

Class I
"1.Clinical seizures should be treated with antiseizure drugs (Level of Evidence: A)"
"2.Patients with a change in mental status who are found to have electrographic seizures on EEG should be treated with antiseizure drugs (Level of Evidence: C)"
Class III (Harm)
"1.Prophylactic antiseizure medication is not recommended (Level of Evidence: B)"
Class IIa
"1.Continuous EEG monitoring is probably indicated in ICH patients with depressed mental status that is out of proportion to the degree of brain injury (Level of Evidence: C)"

Management of Medical Complications: Recommendations

Class I
"1.A formal screening procedure for dysphagia should be performed in all patients before the initiation of oral intake to reduce the risk of pneumonia (Level of Evidence: B)"
Class IIa
"1. Systematic screening for myocardial ischemia or infarction with electrocardiogram and cardiac enzyme testing after ICH is reasonable (Level of Evidence: C)"

ICP Monitoring and Treatment: Recommendations

Class III (Harm)
"1.Corticosteroids should not be administered for treatment of elevated ICP in ICH (Level of Evidence: B)"
Class IIa
"1.Ventricular drainage as treatment for hydrocephalus is reasonable, especially in patients with decreased level of consciousness (Level of Evidence: B)"
Class IIb
"1. Patients with a GCS score of ≤8, those with clinical evidence of transtentorial herniation, or those with significant IVH or hydrocephalus might be considered for ICP monitoring and treatment. A CPP of 50 to 70 mm Hg may be reasonable to maintain depending on the status of cerebral autoregulation (Level of Evidence: C)"

IVH: Recommendations

Class IIb
"1.Although intraventricular administration of rtPA in IVH appears to have a fairly low complication rate, the efficacy and safety of this treatment are uncertain (Level of Evidence: B)"
"2.The efficacy of endoscopic treatment of IVH is uncertain (Level of Evidence: B)"

References

  1. ↑ Schulman S, Bijsterveld NR. Anticoagulants and their reversal. Transfus Med Rev. 2007;21:37–48. doi: 10.1016/j.tmrv.2006.08.002.
  2. ↑ Andrews CM, Jauch EC, Hemphill JC 3rd, Smith WS, Weingart SD. Emergency neurological life support: intracerebral hemorrhage. Neurocrit Care. 2012;17(suppl 1):S37–S46. doi: 10.1007/s12028-012-9757-2.
  3. ↑ Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, Svensson PJ, Veenstra DL, Crowther M, Guyatt GH; American College of Chest Physicians. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e152S–e184S. doi: 10.1378/ chest.11-2295.
  4. ↑ Hanley JP. Warfarin reversal. J Clin Pathol. 2004;57:1132–1139. doi: 10.1136/jcp.2003.008904.
  5. ↑ Kaatz S, Kouides PA, Garcia DA, Spyropolous AC, Crowther M, Douketis JD, Chan AK, James A, Moll S, Ortel TL, Van Cott EM, Ansell J. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol. 2012;87 Suppl 1:S141–S145. doi: 10.1002/ ajh.23202.
  6. ↑ Dager WE, Gosselin RC, Roberts AJ. Reversing dabigatran in life-threat- ening bleeding occurring during cardiac ablation with factor eight inhibi- tor bypassing activity. Crit Care Med. 2013;41:e42–e46. doi: 10.1097/ CCM.0b013e31827caaa3.
  7. ↑ Oh JJ, Akers WS, Lewis D, Ramaiah C, Flynn JD. Recombinant factor VIIa for refractory bleeding after cardiac surgery secondary to antico- agulation with the direct thrombin inhibitor lepirudin. Pharmacotherapy. 2006;26:569–577. doi: 10.1592/phco.26.4.576.
  8. ↑ Veshchev I, Elran H, Salame K. Recombinant coagulation factor VIIa for rapid preoperative correction of warfarin-related coagulopathy in patients with acute subdural hematoma. Med Sci Monit. 2002;8:CS98–CS100.
  9. ↑ Sansing LH, Messe SR, Cucchiara BL, Cohen SN, Lyden PD, Kasner SE; CHANT Investigators. Prior antiplatelet use does not affect hem- orrhage growth or outcome after ICH. Neurology. 2009;72:1397–1402. doi: 10.1212/01.wnl.0000342709.31341.88.
  10. ↑ Naidech AM, Jovanovic B, Liebling S, Garg RK, Bassin SL, Bendok BR, Bernstein RA, Alberts MJ, Batjer HH. Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerebral hemorrhage. Stroke. 2009;40:2398–2401. doi: 10.1161/ STROKEAHA.109.550939.
  11. ↑ de Gans K, de Haan RJ, Majoie CB, Koopman MM, Brand A, Dijkgraaf MG, Vermeulen M, Roos YB; PATCH Investigators. PATCH: Platelet Transfusion in Cerebral Haemorrhage: study protocol for a multi- centre, randomised, controlled trial. BMC Neurol. 2010;10:19. doi: 10.1186/1471-2377-10-19.
  12. ↑ Naidech AM, Bernstein RA, Levasseur K, Bassin SL, Bendok BR, Batjer HH, Bleck TP, Alberts MJ. Platelet activity and outcome after intracerebral hemorrhage. Ann Neurol. 2009;65:352–356. doi: 10.1002/ ana.21618.
  13. ↑ Gregory PC, Kuhlemeier KV. Prevalence of venous thromboembolism in acute hemorrhagic and thromboembolic stroke. Am J Phys Med Rehabil. 2003;82:364–369. doi: 10.1097/01.PHM.0000064725.62897.A5.
  14. ↑ Dennis M, Sandercock P, Reid J, Graham C, Forbes J, Murray G; CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial [published corrections appear in Lancet. 2013;382:506 and Lancet. 2013;382:1020]. Lancet. 2013;382:516–524. doi: 10.1016/S0140-6736(13)61050-8.
  15. ↑ Kelly J, Hunt BJ, Lewis RR, Rudd A. Anticoagulation or inferior vena cava filter placement for patients with primary intracerebral hemorrhage developing venous thromboembolism? Stroke. 2003;34:2999–3005. doi: 10.1161/01.STR.0000102561.86835.17.
  16. ↑ van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359–1367.
  17. ↑ Middleton S, McElduff P, Ward J, Grimshaw JM, Dale S, D’Este C, Drury P, Griffiths R, Cheung NW, Quinn C, Evans M, Cadilhac D, Levi C; QASC Trialists Group. Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial. Lancet. 2011;378:1699–1706. doi: 10.1016/S0140-6736(11)61485-2.
  18. ↑ Broessner G, Beer R, Lackner P, Helbok R, Fischer M, Pfausler B, Rhorer J, Küppers-Tiedt L, Schneider D, Schmutzhard E. Prophylactic, endovascularly based, long-term normothermia in ICU patients with severe cerebrovascular disease: bicenter prospective, randomized trial. Stroke. 2009;40:e657–e665. doi: 10.1161/STROKEAHA.109.557652.
  19. ↑ Wolfe TJ, Torbey MT. Management of intracranial pressure. Curr Neurol Neurosci Rep. 2009;9:477–485.
  20. ↑ Kamel H, Navi BB, Nakagawa K, Hemphill JC, Ko NU (2011). "Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials". Crit Care Med. 39 (3): 554–9. doi:10.1097/CCM.0b013e318206b9be. PMID 21242790.
  21. ↑ Poungvarin N, Bhoopat W, Viriyavejakul A, Rodprasert P, Buranasiri P, Sukondhabhant S; et al. (1987). "Effects of dexamethasone in primary supratentorial intracerebral hemorrhage". N Engl J Med. 316 (20): 1229–33. doi:10.1056/NEJM198705143162001. PMID 3574383.
  22. ↑ Castaño Ávila S, Corral Lozano E, Vallejo De La Cueva A, Maynar Moliner J, Martín López A, Fonseca San Miguel F, Urturi Matos JA, Manzano Ramírez A. Intraventricular hemorrhage treated with intraven- tricular fibrinolysis: a 10-year experie
  23. ↑ King NK, Lai JL, Tan LB, Lee KK, Pang BC, Ng I, Wang E. A ran- domized, placebo-controlled pilot study of patients with spontaneous intraventricular haemorrhage treated with intraventricular thrombolysis. J Clin Neurosci. 2012;19:961–964. doi: 10.1016/j.jocn.2011.09.030.
  24. ↑ 2015 AHA/ASA Guidelines for the Management of Spontaneous Intracerebral Hemorrhage http://stroke.ahajournals.org/content/early/2015/05/28/STR.0000000000000069 Accessed on November 10, 2016


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