Treating Blood Pressure in Intracranial Hemorrhage

hemorrhagic stroke equal podcast

Blood pressure control in the setting of ischemic stroke has a clearly recognized benefit in patient outcomes. The impact of blood pressure control in hemorrhagic stroke is not as well understood. The ACEP E-QUAL Network podcast, a partnership with ALiEM to promote clinical practice improvements, reviewed this topic with Dr. Latha Ganti (University of Central Florida College of Medicine). Dr. Ganti addressed the evidence behind recommended blood pressure targets and the available medications to achieve control. We present highlights from this discussion with Dr. Jason Woods.

 

What is the goal of blood pressure control in hemorrhagic stroke?

Management of blood pressure in intracranial hemorrhage (ICH) raises questions about the benefit of limiting hematoma expansion while maintaining cerebral perfusion. While it seems intuitive that hypertension should be controlled to limit hematoma expansion, patients with hemorrhagic stroke may be dependent on higher blood pressures for adequate perfusion.

Does lowering blood pressure lead to perihematomal ischemia?

ICH Adapt studies did not show evidence of decreased cerebral blood flow in perihematomal tissue and demonstrated that there is likely preservation of autoregulation which prevents ischemia [1].

Does lowering BP help prevent hematoma expansion and improve outcomes?

The risk of hematoma expansion is highest within the first couple of hours following initial bleeding. Hematoma expansion is clearly associated with worse outcomes. Scoring tools exist to estimate the risk of hematoma expansion. The “spot sign,” seen on source images from a computed tomography angiogram of the brain, suggests an area of dynamic bleeding.

  • ICH ADAPT: no difference in hematoma expansion or clinical outcome with acute blood pressure lowering [2].
  • INTERACT 2: intensive lowering of blood pressure did not result in a significant reduction in mortality or severe disability [3].
  • ATACH 2: intensive lowering of blood pressure did not improve functional outcomes but was associated with increased renal dysfunction [4].

What is the optimal systolic blood pressure (SBP) target?

AHA Guidelines 2015

  • ICH patients with SBP 150-220 mmHg, lower to 14 mmHg is safe
  • ICH patients with SBP > 220 mmHg, aggressive reduction with continuous infusion may be reasonable

So what’s the right thing to do? If data suggests that lowering may not be as beneficial, what should the target blood pressure be?

  • Target SBP 140-160 mmHg is a reasonable target

What medications are preferred for blood pressure control in ICH?

The ideal agent for blood pressure management in ICH would have a quick onset, but short duration, to allow titration.

Recommended first-line:

  • Labetalol
    • Onset < 5 min
    • Duration of effect 2-4 hr
    • IV bolus dose: 20 mg, followed by 20-80 mg every 10 min to a total dose of 300 mg.
    • Infusion dose: 0.5 mg-2 mg/min
    • Avoid in: asthma, COPD, heart failure, AV block
  • Nicardipine
    • Onset 1-2 min
    • Half-life ~ 40 min
    • Infusion dose: 0.5-1 mcg/kg/min, max 3 mcg/kg/min
  • Clevidipine
    • Onset 1-4 min
    • Duration of effect 5-15 min
    • Infusion dose: 1 mg/hr, up to 21 mg/hr, titrate by 2.5 mg/hr every 5-10 min
    • Avoid in: severe aortic stenosis, and lipid metabolism dysfunction or known allergy to eggs or soy (delivered as lipid emulsion)

Available second-line (mostly off-label, not preferred)

  • Esmolol
  • Fenoldopam
  • Hydralazine
  • Enalaprilat

Conclusions

When it comes to blood pressure: keep it simple.

  • Target SBP 140-160 mmHg
  • Top three drugs: Labetalol, Nicardipine, Clevidipine

Although labetalol has common contraindications, it is available as a bolus dose. In a clinical setting where drips may not be readily available, Labetalol can be easier to get.

Interested in more ACEP-EQUAL podcasts?

Listen to the other ACEP E-QUAL podcasts on our Soundcloud account.

References

  1. Butcher K, Jeerakathil T, Emery D, et al. The Intracerebral Haemorrhage Acutely Decreasing Arterial Pressure Trial: ICH ADAPT. Int J Stroke. 2010;5(3):227-233. PMID: 20536619
  2. Butcher KS, Jeerakathil T, Hill M, et al. The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial. Stroke. 2013;44(3):620-626. PMID: 23391776
  3. Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368(25):2355-2365. PMID: 23713578
  4. Qureshi AI, Palesch YY, Barsan WG, et al. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med. 2016;375(11):1033-1043. PMID: 27276234
By |2020-10-09T09:47:57-07:00Oct 23, 2020|Academic, Emergency Medicine, Neurology|

Anticoagulant Reversal in Hemorrhagic Stroke

anticoagulant equal podcast

Acute management of cerebrovascular accidents can be challenging enough, but questions about anticoagulant reversal in the setting of hemorrhagic stroke add another layer of complexity. The ACEP E-QUAL Network podcast, a partnership with ALiEM to promote clinical practice improvements, reviewed this topic with Dr. Joshua Goldstein (Massachusetts General Hospital, Harvard Medical School). Dr. Goldstein addressed common anticoagulants and their reversal agents, summarizing available literature to inform clinical practice. We present highlights from this discussion with Dr. Jason Woods.

 

What is the goal of anticoagulant reversal?

Since it is impossible to go back in time to prevent intracranial hemorrhage (ICH), the focus of management for hemorrhagic stroke should be to prevent further bleeding and allow brain tissue an opportunity to recover. The goal of anticoagulant reversal in patients with ICH is to decrease ongoing bleeding.

Warfarin

Warfarin is a vitamin K antagonist. Since vitamin K is required for the processing of coagulation factors II, VII, IX, and X, patients on warfarin have decreased amounts of these factors in circulation. To increase the availability of these factors, countering the effect of warfarin therapy can be two-fold:

  1. Replenish vitamin K to allow the production of new factors.
  2. Provide replacement of these factors directly.

Vitamin K supplementation will not provide immediate effect, and it may take up to 24 hours for the production of new coagulation factors. While it should be given early, patients also require factor replacement acutely.

Fresh frozen plasma (FFP) or prothrombin complex concentrate (PCC) can be given to supplement coagulation factors.

  • FFP carries each of the 4 needed factors in addition to other clotting factors.
    • The cost of FFP is low.
    • Transfusion will take some time as it will require ~ 1 L volume.
  • PCC, marketed as Kaycentra in the US, consists of concentrated Factor II, VII, IX, X, and proteins C and S.
    • The cost of PCC is higher.
    • Transfusion is quick, ~70 mL, and leads to rapid correction of INR.

Studies have shown PCC to be associated with faster INR reversal, less ICH expansion, and a non-statistical trend toward decreased mortality [1]. PCC does carry a theoretical risk of thromboembolism given the rapid correction, but no evidence exists to suggest that this is the case.

Direct Oral Anticoagulants (DOACs)

There are 2 categories of DOACs:

  1. Factor II inhibitors (e.g., dabigatran)
  2. Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban)

Approach to reversal: remove the inhibitor to allow normal function of already existent Factor II or Xa

  • Time
    • Time can be thought of as a reversal agent. Most DOACs have a half-life ~12 hours. If the timing of the last dose is known and it was hours ago, there may not be much medication left to reverse.
  • Monoclonal antibodies
    • Reversal of dabigatran can be achieved with the use of a monoclonal antibody, idarucizumab, to bind up circulating inhibitor.
    • Reversal of Factor Xa inhibitors can similarly be attempted with the use of monoclonal antibody andexanet. Andexanet is notably more expensive than idarucizumab.
  • PCC
    • PCC can be used off-label to outcompete circulating inhibitor with extra coagulation factors and increase the number of functional factors.

It should be noted that there are no reliable tests for measuring DOAC activity.

Dual Antiplatelet Therapy (DAPT)

The most common agents are aspirin and Plavix (clopidogrel). The issue with patients on these antiplatelet agents is not a lack of platelets, but the presence of medication that suppresses normal platelet function. Theoretically, if one could provide extra platelets, the inhibiting agent could be saturated and the remaining platelets provide some functional activity.

The PATCH trial demonstrated, however, that platelet transfusion led to significantly worse outcomes [2]. While there is no readily available reversal agent for DAPT, platelet transfusion should be avoided. In fact, observational data suggest that patients on single antiplatelet therapy don’t fare worse and may not need reversal like those with DAPT [3].

Conclusions

Warfarin reversal

  • IV vitamin K + PCC (or FFP)

Dabigatran reversal

  • Specific agent: Idarucizumab
  • Non-specific agent: PCC

Factor Xa inhibitor reversal

  • Specific agent: Andexanet
  • Non-specific agent: PCC

Antiplatelet reversal

  • No available agent
  • Transfusion of platelets associated with worse outcomes.

Interested in more ACEP-EQUAL podcasts?

Listen to the other ACEP E-QUAL podcasts on our Soundcloud account.

References

  1. Steiner T, Poli S, Griebe M, et al. Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial. Lancet Neurol. 2016;15(6):566-573. [PMID: 27302126]
  2. Baharoglu MI, Cordonnier C, Al-Shahi Salman R, et al. 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(10038):2605-2613. [PMID:27178479]
  3. Khan NI, Siddiqui FM, Goldstein JN, et al. Association Between Previous Use of Antiplatelet Therapy and Intracerebral Hemorrhage Outcomes. Stroke. 2017;48(7):1810-1817. [PMID:28596454]
By |2020-10-09T09:33:43-07:00Oct 16, 2020|Academic, Emergency Medicine, Neurology|

IDEA Series: 3D-printed pediatric lumbar puncture trainer

Pediatric lumbar puncture trainers are less available than adult trainers; most are the newborn size and quite expensive. Due to age-based practice patterns for fever diagnostic testing, most pediatric lumbar punctures are performed on young infants, and residents have fewer opportunities to perform lumbar punctures on older children.1 Adult lumbar puncture trainers have been created using a 3D-printed spine and ballistics gel, which allows for ultrasound guidance.2 No previous model has been described for pediatric lumbar puncture.

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SAEM Clinical Image Series: Found Down with Altered Mental Status

non-contrast head CT

A forty-nine-year-old male with a history of polysubstance abuse, including methamphetamine and intravenous (IV) drug use, rectal cancer, and human immunodeficiency virus (HIV) was brought into the emergency department by emergency medical services (EMS) after he was found down at the bottom of a flight of stairs by his roommate. In the emergency room, he was found to have a Glasgow Coma Scale (GCS) score of 7 and was intubated for airway protection. Non-contrast head CT was performed. Per the roommate, the patient had been “not himself,” exhibiting strange behavior and weight loss. History and review of systems (ROS) were otherwise unobtainable due to the acuity of illness.

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SAEM Clinical Image Series: Double Vision

cranial nerve palsy CN3

Chief complaint: Double vision

History of Present Illness: 61 year old female with history of HTN, DM, hyperlipidemia, and chronic low back pain presenting with double vision. She received an epidural spinal injection yesterday for the 4th time for low back pain. She was sedated for the procedure and woke up with headache, neck stiffness, and left eye “jumping around,” which progressed to double vision 1 hour later.

There was no blurry or double vision with either eye closed. She had 1 episode of emesis. She presented to the ED 24 hours later with continued headache and double vision.

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By |2019-10-30T21:13:07-07:00Oct 14, 2019|Neurology, Ophthalmology, SAEM Clinical Images|

SAEM Clinical Image Series: Young Woman with a Headache

Headache

[Click for larger view]

Chief complaint: Headaches for 1 year

History of Present Illness: A 31-year-old woman with no significant past history presents with a dull headache.

She notes the headache is generalized, has been almost daily for a year and is worsened by bending over. She denies nausea, vomiting, photophobia, trauma, seizures, focal weakness, numbness, or vision change. Acetaminophen and ibuprofen provide only mild, short-acting relief. She takes oral birth control and her periods have been normal.

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ALiEM AIR | Neurology 2019 Module

Welcome to the Neurology Module! After carefully reviewing all relevant posts from the top 50 sites of the Social Media Index, the ALiEM AIR Team is proud to present the highest quality online content related to neurological emergencies. 6 blog posts within the past 12 months (as of January 2019) met our standard of online excellence and were curated and approved for residency training by the AIR Series Board. We identified 1 AIR and 5 Honorable Mentions. We recommend programs give 3 hours (about 30 minutes per article) of III credit for this module. (more…)

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