Hemorrhagic Stroke Guideline Summary for ICU

                               MCC ICU Topic Deep Dive: Hemorrhagic Stroke 

Definition: Hemorrhage into the brain parenchyma or subarachnoid space as the result of an aneurysm rupture. 

Common Risk Factors: Hypertension, hyperlipidemia, head trauma, smoking, alcohol abuse, diabetes, liver disease, drug abuse, brain tumor,  cerebral aneurysm, arteriovenous malformation, anticoagulant use, cerebral amyloidopathy, genetics, race, age, history of previous ischemic or hemorrhagic stroke, vasoactive drugs including triptans, SSRIs, decongestants, stimulants, phentermine, sympathomimetic drugs

Symptoms: Sudden headache, confusion, dizziness, slurred speech, aphasia, visual loss or disturbance, focal weakness, sensation loss, seizure, ataxia, altered level of consciousness. 

Pharmacologic Treatment: Antihypertensive medication, anticoagulant reversal, hypertonic therapy, pain medication 

Nonpharmacologic: Elevated HOB (30 degrees or more), external ventricular drain, hemicraniectomy, hematoma evacuation

A Brief ICU Focused Guideline: American Heart Association/American Stroke Association (2022) 

• In patients with spontaneous ICH, focused history, physical examination, and routine laboratory work and tests on hospital admission (eg, complete blood count, prothrombin time/ international normalized ratio [INR]/partial thromboplastin time, creatinine/estimated glomerular filtration rate, glucose, cardiac troponin and ECG, toxicology screen, and inflammatory markers) should be performed to help identify the type of hemorrhage, active medical issues, and risk of unfavorable outcomes.
• In patients with spontaneous ICH and/or IVH, serial head CT can be useful within the first 24 hours after symptom onset to evaluate for hemorrhage expansion
• In patients with lobar spontaneous ICH and age <70 years, deep/posterior fossa spontaneous ICH and age <45 years, or deep/ posterior fossa and age 45 to 70 years without history of hypertension, acute CTA plus consideration of venography is recommended to exclude macrovascular causes of cerebral venous thrombosis
• In patients with spontaneous IVH and no detectable parenchymal hemorrhage, catheter intra-arterial digital subtraction angiography (Cerebral Angiogram) is recommended to exclude a macrovascular cause
• For patients with ICH who arrive with a blood pressure of 150-220, aggressive blood pressure management to less than SBP 140 and a goal range of SBP 130-150 is recommended
• For patients with large or severe ICH and requirement of surgical intervention, the safety and efficacy of aggressive blood pressure lowering is unknown
• Lowering of blood pressure below SBP of 130 is potentially harmful 
• Anticoagulation should be discontinued immediately and rapid reversal of anticoagulation should be performed as soon as possible after diagnosis of spontaneous ICH to improve survival’
• For patients with ICH and treatment with aspirin prior to arrival AND the need for emergent neurosurgery, the use of platelets may be considered to reduce post operative bleeding and improve mortality 
• For patients with ICH and treatment with aspirin prior to arrival, it is unclear if there is any benefit to using desmopressin with or without platelet transfusions to reduce expansion of the hematoma. 
• For patients with spontaneous ICH being treated with aspirin and not scheduled for emergency surgery, platelet transfusions are potentially harmful and should not be administered
• In patients with spontaneous ICH and clinical hydrocephalus, transfer to centers with neurosurgical capabilities for definitive hydrocephalus management (eg, EVD placement and monitoring) is recommended to reduce mortality
• For warfarin or DOAC reversal, 4 Factor PCC may be used in facilities that do to have FDA approved alternatives

• In non ambulatory patients with ICH, the use of unfractionated heparin or low molecular weight heparin may be reasonable to prevent DVT 24-48 hours after ICH onset. 
• For patients with ICH and confirmed PE or DVT, delaying treatment with LMWH or UFH for 1-2 weeks may be reasonable. 
• In patients with ICH and without clinical seizures, there is no benefit to prophylactic seizure treatment to improve mortality, improve functional outcomes, or control seizures long term. 
• In patients with ICH, the benefit of prophylactic hypertonic therapy to improve outcomes is unknown 
• In patients with ICH, hypertonic therapy may be considered to transiently reduce ICP 
• Do not use steroids for ICP treatment in patients with ICH 
• For patients with spontaneous ICH, large Intraventricular Hemorrhage, and impaired level of consciousness, EVD placement is recommended in preference to medical management alone to reduce mortality. 

We generally do not have much say in the surgical management of these patients, but below are the recommendations. 

• For most patients with spontaneous supratentorial ICH of moderate to greater severity, the usefulness of craniotomy for hemorrhage evacuation to improve functional outcomes or mortality is not clear. 
• For patients with cerebellar ICH who are deteriorating neurologically, have brain stem compression and/or ventricular obstruction or have cerebellar ICH volume of > 14 ml, immediate surgical removal with or without EVD is recommended in preference to medical management alone to reduce mortality. 
• For patients with large supratentorial IVH who are in a coma, have a large hematoma (> 30 ml) with significant midline shift, or have elevated ICP refractory to medical management, decompressive craniotomy with or without hematoma evacuation may be considered to reduce mortality. It is uncertain if this improves functional outcomes. 
• In patients with spontaneous ICH, a baseline severity score should be obtained as part of the initial work up. A baseline severity score should not be used as the sole basis for forecasting an individual prognosis or limiting life sustaining treatment. 
• In patients without pre-exisiting documented goals of care, postponing new withdrawal of care or new DNR orders should not be enacted before the second full day of treatment to improve mortality and functional outcome. 
• In patients with ICH and moderate to severe depression, the use of appropriate evidence based treatments including psychotherapy and pharmacotherapy are useful to reduce depression 
• Continuation or initiation of SSRI’s can be beneficial for the treatment of mood disorders. 
• In patients with ICH and high risk of thromboembolic events (LVAD, mechanical valve), early resumption of anticoagulation to prevent thrombotic complications is reasonable. 
• In patients with spontaneous ICH and an indication for antiplatelet treatment, resumption of antiplatelet treatment may be reasonable based on risk/benefit analysis.
• For patients with atrial fibrillation and spontaneous ICH that choose to resume anticoagulation, a period of 7-8 weeks is a reasonable timeline to resume treatment. Alternatively, left atrial appendage closure may be considered. 
• For patients with an indication for statin treatment the risks and benefits of statin therapy on ICH outcomes and recurrence relative to overall prevention of cardiovascular events are uncertain.  
• Long term use of NSaids after spontaneous ICH is potentially harmful. 
• 
  

   Pharmacological options surrounding treatment of spontaneous intracranial hemorrhage.

Reversal Agents: 

Four Factor Prothrombin Concentrate (PCC): Combination of clotting factor II, VII, IX, X. IV only. Originally designed for warfarin reversal and now used as an alternative for NOAC reversal (apixaban, Xarelto, Pradaxa). Onset of action is several minutes. Dosing for warfarin is based on INR values. Dosing for NOAC reversal is weight based. 

Andexxa: Binds to factor X inhibitors and promotes thrombin generation.  FDA approved for reversal of Eliquis and Xarelto. Onset of action is several minutes. Extremely expensive on not on formulary at many facilities. 

Praxbind: Binds to dabigatran and its metabolites. FDA approved for reversal of Pradaxa. Anticoagulant effect of Pradaxa is neutralized immediately. 

Protamine: Actively binds to heparin and reverses the anticoagulation effect. FDA approved for reversal of heparin. This has a similar effect on lovenox but may need to be dosed more than once if lovenox was the instigating agent. Dosing is based directly on the dose of heparin that was being used. Onset of action is within minutes. 

Hypertonic Agents: 

Sodium Chloride: Available as 1.8%, 3% IV infusions or 23.4% IVP. For 23.4% (Osmolarity 8008 mOsmol/L) solutions central lines are a necessity. Dosing is generally titrated to effect. Traditionally q4 hours sodium levels are drawn with a goal of either 145-150 mmol/L for moderate ICP concern or 150-155 mmol/L for severe ICP concern. 

Mannitol: For ICP emergencies, doses range from 0.25 - 2.0 g per kg as a one time IVPB over 15-30 minutes. Mannitol is a supersaturated sugar solution that results in a high osmolarity gradient and is renally cleared as an unchanged medication. Maintenance dosing is typically 12.5 grams or 25 grams every 6 hours with serum osmolality lab draws and a hold parameter of serum osmol  > 320. I/O should be accurately recorded 

Random Dan Advice: 

• Traumatic subarachnoid hemorrhages, epidural hematomas, and both spontaneous or traumatic subdural hematomas are not hemorrhagic strokes. You are not bound by the hemorrhagic stroke order set for these patients, but treatment is extremely similar and it is not wrong to use. 
• There is no such thing as seizure prophylaxis for hemorrhagic stroke patients. Save seizure medications for patients that are having seizures. 
• Hypertonic decisions should be based on ICP concerns. An alert patient with a headache does not necessarily need hypertonic. A patient that previously was awake and is now lethargic or obtunded with cerebral edema on a CT scan is a better candidate. 
• Mannitol or hypertonic saline are equivalent in stroke research and neither of these have amazing evidence to support them. Try not to mix and match; just pick one and go with it. 
• The real goal of hypertonic treatment is not to raise the patient’s sodium. You are trying to pull water from cells and shrink the patient’s brain to lower their ICP. There is no need to worry about a subtherapeutic sodium level in a patient that wakes up or improves after your treatment. 
• If a neurosurgeon is asking for something that you disagree with please defer to your attending provider for help and consider a neurology consult if needed. Not everyone follows the guidelines, nor are they always obligated to do what a guideline says. 
• Neuro checks are great to have, but patients with pain and agitation will have a higher ICP than a calm and comfortable patient. There is a balance to be achieved her

Recent evidence for/against some of the above 

Moullaali TJ, Wang X, Martin RH, Shipes VB, Robinson TG, Chalmers J, Suarez JI, Qureshi AI, Palesch YY, Anderson CS. Blood pressure control and clinical outcomes in acute intracerebral haemorrhage: a preplanned pooled analysis of individual participant data. Lancet Neurol. 2019;18:857–864. doi: 10.1016/S1474-4422(19)30196-6

Wang X, Arima H, Heeley E, Delcourt C, Huang Y, Wang J, Stapf C, Robinson T, Woodward M, Chalmers J, et al; INTERACT2 Investigators. Magnitude of blood pressure reduction and clinical outcomes in acute intracerebral hemorrhage: Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial study. Hypertension. 2015;65:1026–1032. doi: 10.1161/HYPERTENSIONAHA.114.05044

Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C, Lindley R, Robinson T, Lavados P, Neal B, et al; INTERACT2 Investigators. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368:2355–2365. doi: 10.1056/NEJMoa1214609

Qureshi AI, Palesch YY, Barsan WG, Hanley DF, Hsu CY, Martin RL, Moy CS, Silbergleit R, Steiner T, Suarez JI, et al; ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med. 2016;375:1033–1043. doi: 10.1056/NEJMoa1603460

Baharoglu MI, Cordonnier C, Al-Shahi Salman R, de Gans K, Koopman MM, Brand A, Majoie CB, Beenen LF, Marquering HA, Vermeulen M, et al; PATCH Investigators. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. Lancet. 2016;387:2605–2613. doi: 10.1016/S0140-6736(16)30392-0

Boeer A, Voth E, Henze T, Prange HW. Early heparin therapy in patients with spontaneous intracerebral haemorrhage. J Neurol Neurosurg Psychiatry. 1991;54:466–467. doi: 10.1136/jnnp.54.5.466

Faust AC, Finch CK, Hurdle AC, Elijovich L. Early versus delayed initiation of pharmacological venous thromboembolism prophylaxis after an intracranial hemorrhage. Neurologist. 2017;22:166–170. doi: 10.1097/NRL.0000000000000141

Ianosi B, Gaasch M, Rass V, Huber L, Hackl W, Kofler M, Schiefecker AJ, Addis A, Beer R, Rhomberg P, et al. Early thrombosis prophylaxis with enoxaparin is not associated with hematoma expansion in patients with spontaneous intracerebral hemorrhage. Eur J Neurol. 2019;26:333–341. doi: 10.1111/ene.13830

Angriman F, Tirupakuzhi Vijayaraghavan BK, Dragoi L, Lopez Soto C, Chapman M, Scales DC. Antiepileptic drugs to prevent seizures after spontaneous intracerebral hemorrhage. Stroke. 2019;50:1095–1099. doi: 10.1161/STROKEAHA.118.024380

Sheth KN, Martini SR, Moomaw CJ, Koch S, Elkind MS, Sung G, Kittner SJ, Frankel M, Rosand J, Langefeld CD, et al; ERICH Investigators. Prophylactic antiepileptic drug use and outcome in the Ethnic/Racial Variations of Intracerebral Hemorrhage study. Stroke. 2015;46:3532–3535. doi: 10.1161/STROKEAHA.115.010875

Spoelhof B, Sanchez-Bautista J, Zorrilla-Vaca A, Kaplan PW, Farrokh S, Mirski M, Freund B, Rivera-Lara L. Impact of antiepileptic drugs for seizure prophylaxis on short and long-term functional outcomes in patients with acute intracerebral hemorrhage: a meta-analysis and systematic review. Seizure. 2019;69:140–146. doi: 10.1016/j.seizure.2019.04.017

Zandieh A, Messé SR, Cucchiara B, Mullen MT, Kasner SE; VISTA-ICH Collaborators. Prophylactic use of antiepileptic drugs in patients with spontaneous intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2016;25:2159–2166. doi: 10.1016/j.jstrokecerebrovasdis.2016.05.026

Kamel H, Navi BB, Nakagawa K, Hemphill JC, Ko NU. Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials. Crit Care Med. 2011;39:554–559. doi: 10.1097/CCM.0b013e318206b9be

Tan G, Zhou J, Yuan D, Sun S. Formula for use of mannitol in patients with intracerebral haemorrhage and high intracranial pressure. Clin Drug Investig. 2008;28:81–87. doi: 10.2165/00044011-200828020-00002

Vicenzini E, Ricciardi MC, Zuco C, Sirimarco G, Di Piero V, Lenzi GL. Effects of a single mannitol bolus on cerebral hemodynamics in intracerebral hemorrhage: a transcranial Doppler study. Cerebrovasc Dis. 2011;32:447–453. doi: 10.1159/000330639

Kobayashi S, Sato A, Kageyama Y, Nakamura H, Watanabe Y, Yamaura A. Treatment of hypertensive cerebellar hemorrhage: surgical or conservative management? Neurosurgery. 1994;34:246–250.

Zhou H, Zhang Y, Liu L, Han X, Tao Y, Tang Y, Hua W, Xue J, Dong Q. A prospective controlled study: minimally invasive stereotactic puncture therapy versus conventional craniotomy in the treatment of acute intracerebral hemorrhage. BMC Neurol. 2011;11:76. doi: 10.1186/1471-2377-11-76

Wang W, Zhou N, Wang C. Minimally invasive surgery for patients with hypertensive intracerebral hemorrhage with large hematoma volume: a retrospective study. World Neurosurg. 2017;105:348–358. doi: 10.1016/j.wneu.2017.05.158

Shi J, Cai Z, Han W, Dong B, Mao Y, Cao J, Wang S, Guan W. Stereotactic catheter drainage versus conventional craniotomy for severe spontaneous intracerebral hemorrhage in the basal ganglia. Cell Transplant. 2019;28:1025–1032. doi: 10.1177/0963689719852302