Monthly Archives: October 2015

Beta Blocker Classification

Quick summary of Beta Blockers

beta blockers

β1-receptors: affects heart rate, conduction and contractility

β2-receptors: cause smooth muscle contraction, bronchospasm in predisposed

Classified into three generations

  1. first generation
    • (Propranolol, Sotalol, Timolol, Nadolol)
    • nonselective:  block β1 and β2 receptors.
  2. second-generation agents
    • (Atenolol, Bisoprolol, Celiprolol, Metoprolol)
    • cardioselective agents
    • block β1-receptors in low doses, block β2-receptors in higher doses.
    • more suitable in chronic lung disease or insulin-requiring diabetes mellitus
    • Bisoprolol most selective
  3. third generation agents
    • either selective (Nebivolol) or nonselective (Carvidolol and Labetolol)
    • vasodilatory properties mediated either by nitric oxide release (Nebivolol or Carvedilol) or by alpha-adrenergic blockade (Labetolol and Carvedilol)

B blockers with ISA

  • third vasodilatory mechanism (Pindolol, Acebutolol) acts via β2-intrinsic sympathomimetic activity (ISA)
  • stimulate as well as to block adrenergic receptors
  • cause less bradycardia than the other beta-blockers and may cause less coldness of the extremities.

References

Khaled Albouaini, Mohaned Egred. ‘Beta-Blockers Use In Patients With Chronic Obstructive Pulmonary Disease And Concomitant Cardiovascular Conditions’. International Journal of Chronic Obstructive Pulmonary Disease 2.4 (2007): 535. Web. 23 Oct. 2015.

Inraventricular tPA for Intraventricular Hemorrhage

As neurocritical care intensivists eagerly await the results of CLEAR III trial, many have started to offer intraventricular tissue plasminogen activator (IV-tPA) on an off-label basis to patients who have intraventricular hemorrahges with high clot burden.

This blog reviews the procedure for IV-tPA as used in the CLEAR III trial.

Inclusion.  The study included the following patients:  age 18-80, symptom onset <24h prior to diagnostic CT scan, spontaneous ICH </= 30 cc and IVH obstructing the III and IV ventricles.  Patients with primary IVH were included in the study as well.  Both the ICH and IVH clot must demonstrate stability.  CT scan peformed 6 hours or more after catheter placement must show that the ICH size not differ by </=5cc compared to the previous CT.  Also, the width of the lateral ventricle that is affected most by the clot must not increase by 2mm.

Catheter tract bleeding must be </= 5cc on CT scan.  SBP should be <200 for the 6 hours prior to drug administration.

Exclusion.  The following patients were excluded from the trial:  patients wih suspected aneurysm (untreated), ruptured AVM or tumor, choroid plexus vascular malformatoin or Moyamoya disease, patients with clotting disorders, use of NOACs, platelet <100K, INR <1.4, pregnancy, infratentorial hemorrhage, thalamic bleeds, SAH, ongoing internal bleeding, bleeding at multiple vascular puncture and access sites.  Patients with treated aneurysm or AVM were included if treatment occurred at least 3 months before the current onset.

Intraventricular tPA procedure:

  1. Administer 1.0mg/mL of tPA via the EVD
  2. Flush with sterile saline (4mL) to clear tPA from the catheter
  3. Clamp EVD for 1 hour, and then open to drain clot and CSF until next injection
  4. Continue treatment every 8 hours for up to 12 doses of the drug

Capture

Dual Catheters.  For patients ith dual catheters, alternate the doses through each catheter every eight hours.  Once the III and IV ventricles are open, discontinue dosing via the catheter contralateral to the clot.  Continue  dosing through the ipsilesional ventricle until ~80% of the intraventricular clot has been removed, IVH-related shift has resolved, or a total of 12 doses have been administered.

Maintain ICP  <30 and CPP >70mm Hg.

Order CT scans on days 1-5 and then 1 and 3 days after the last dose of tPA.

CHECKLIST:

  • diagnostic CT
  • diagnostic CTA or routine angiogram
  • EVD placement
  • stability CT
  • BP <200 over 6 hours
  • tox screen
  • go over inclusion and exclusion criteria
  • informed consent
  • start IV-tPA (1.0 mg q8h) up to 12 doses and open to drainx24h after last dose
  • CT scan on Days 1-5 and then 1 and 3 days after last dose
  • lab assessments daily from days 1-7


REFERENCE:

Primary Investigator:  Daniel F.Hanley, MD, NIH/NINDS, Johns Hopkins medical Institutions; CLEAR III:  Clot Lysis:  Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III

Optic Nerve Sheath Diameter

The optic nerve sheath, contiguous with brain dura and containing CSF communicating with cerebral subarachnoid components, can be used as a means of indirectly detecting increased ICP.

Optic nerve is ontogenetically a part of the CNS.  It is surrounded by CSF and dura mater (called the optic nerve sheath or ONS).  The diameter of the optic nerve sheath (or ONSD) changes with variations in intracranial pressure.

Ultrasound measurement of the ONSD is a reliable means of detecting elevated ICP in patients with spontaneous intracerebral hemorrhage.  However, ONSD measurements are still not considered as a substitute for invasive ICP monitoring in critical care.

ONSD ONS

By measuring the anterior part of the optic nerve, specifically 3 mm behind the globe, ONSD can be measured via ultrasound with 5-mm ONSD roughly translating to an ICP of 20.

Method:

  1. use a linear ultrasound probe (7.5-MHz) over the upper closed eyelid
  2. keep HOB 30-45 degrees
  3. measure the ONSD 3mm behind the globe (take 2 measurements for each optic nerve sheath, sagittal and transverse)

ONSD cut off for elevated ICP:

  1. 5.7 mm       [Sn 93%, Sp 96%]
  2. 5-5.7 mm    [Sp 83%]

ONSD

 

 

NOTES:

  • Inter/intraobserver not a limiting factor
  • ONSD variation dependent on individual factors such as age and underlying pathology
  • difficult to create an absolute ONSD cutoff value for ICP crises

References

Girisgin, A. S. et al. ‘The Role Of Optic Nerve Ultrasonography In The Diagnosis Of Elevated Intracranial Pressure’. Emergency Medicine Journal 24.4 (2007): 251-254. Web. 23 Oct. 2015.

Moretti, Riccardo et al. ‘Reliability Of Optic Nerve Ultrasound For The Evaluation Of Patients With Spontaneous Intracranial Hemorrhage’. Neurocritical Care 11.3 (2009): 406-410. Web. 23 Oct. 2015.

Roh, David and Soojin Park. “Brain Multimodality Monitoring: Updated Perspectives”. Current Neurology and Neuroscience Reports 16.6 (2016): n. pag. Web.

Glycoprotein IIb/IIIa and Its Inhibitors

Glycoprotein IIb/IIIa

  • AKA integrin αIIbβ3
  • integrin complex found on platelets
  • a receptor for fibrinogen and vWF
  • aids platelet activation

Drugs Targeting Glycoprotein IIb/IIIa

  1. abciximab
  2. eptifibatide
  3. tirofiban

gp2b3a table

Mechanism of action

ADP, etc. activates platelet which leads to conformational change in platelet gpIIb/IIIa receptors (activated member receptor complex) that induces binding to fibrinogen (Factor I), resulting in platelets sticking together – a clot; coagulation cascade stabilizes the clot as thrombin (Factor IIa) converts soluble fibrinogen into insoluble fibrin strands which are cross-linked by Factor XIII to form a stable blood clot

gp2b3a

Pathology related to Glycoprotein IIb/IIIa:

  • GLanzmann’s thrombasthenia – defects in glycoprotein IIb/IIIa
  • ITP – autoantibodies against glycoprotein IIb/IIIa

References

Slideshare.net,. ‘Cardiovascular Drugs’. N.p., 2015. Web. 19 Oct. 2015.

Wikipedia,. ‘Glycoprotein Iib/Iiia’. N.p., 2015. Web. 14 Oct. 2015.

Img.medscape.com,. N.p., 2015. Web. 19 Oct. 2015.

Perimesencephalic Subarachnoid Hemorrhage

PM NASAH

CAUSES OF PERIMESENCEPHALIC SAH

in 2-9% – cause is a ruptured sacular aneurysm, from posterior circulation (basilar tip, vertebrobasilar junction, PICA, SCA or PCA)

In majority, etiology is not defined = PM-NASAH (Perimesencephalic Non-aneurysmal SAH).

Theories for origin of these cases include:

  1. rupture of a perforating artery
  2. venous bleed
  3. basilar artery wall hematoma

RUPTURE OF PERFORATING ARTERY

  • HTN is a risk factor for perforating artery disease, as well as for PM-NASAH
  • location consistent with bleeding from perforating artery arising from posterior circulation

VENOUS ORIGIN

  • suggested by limited extension of blood and low rate of rebleeds – source of bleed is low pressure
  • also, PM-NASAH often occurs in setting of physical exertion – increases intrathoracic pressure – impairs jugular venous return – elevates ICP – leakage of venous blood
  • higher incidence of primitive venous drainage on venography – basal vein of Rosenthal and/or perimesencephalic veins drain directly into dural sinus rather than vein of Galen – more susceptible to venous congestion

BASILAR ARTERY WALL HEMATOMA

  • abnormal contour of basilar artery observed – small bulge or luminal narrowing – ?intramural hematoma as source of bleed?
  • rupture of vasa vasorum is source of limited bleeding

Other Potential Causes of PM-NASAH

  • rupture of cryptic vascular malformation
  • high cervical spinal dural AVF
  • cavernous angioma
  • capillary telangiectasia
  • occult aneurysm

References

Uptodate.com,. ‘Perimesencephalic Nonaneurysmal Subarachnoid Hemorrhage’. N.p., 2015. Web. 16 Oct. 2015.

Aminocaproic Acid in Subarachnoid Hemorrhage

aca aca2

Acute bleeding: Oral, IV: Loading dose: 4-5 g during the first hour, followed by 1 g/hour for 8 hours (or 1.25 g/hour using oral solution) or until bleeding controlled (maximum daily dose: 30 g)

STUDIES USED:  

  1. 5 g bolus followed by 1 g/h for a maximum duration of 48 h.
  2. Epsilon amino-caproic acid, dosage probably 24 g per day (6 times 4 g) orally

How does aminocaproic acid work?

ACA binds competitively to plasminogen; blocking the binding of plasminogen to fibrin and the subsequent conversion to plasmin, resulting in inhibition of fibrin degradation (fibrinolysis)

amicar vs tpa MOA ACA TXA

What do the guidelines say about the use of ACA in SAH?

  • shown to reduce incidence of rebleeding with delay in aneurysm obliteration
  • study one center used short-term ACA to prevent rebleeding during patient transfer, results – decreased in rebleeding, no increase in risk of DCI, 3-month clinical outcomes not affected
  • increased risk of DVT but not PE
  • Note:  neither ACA nor TXA is FDA approved for prevention of aneurysm rebleeding

AHA/ASA Guidelines Recommend:

#3 For patients with an unavoidable delay in obliteration of aneurysm, a significant risk of rebleeding, and no compelling medical contraindications, short-term (<72 hours) therapy with tranexamic acid or aminocaproic acid is reasonable to reduce the risk of early aneurysm rebleeding (Class IIa; Level of Evidence B)

References

Connolly, E. S. et al. ‘Guidelines For The Management Of Aneurysmal Subarachnoid Hemorrhage: A Guideline For Healthcare Professionals From The American Heart Association/American Stroke Association’. Stroke 43.6 (2012): 1711-1737. Web. 15 Oct. 2015.

Foreman, Paul M. et al. ‘Antifibrinolytic Therapy In Aneurysmal Subarachnoid Hemorrhage Increases The Risk For Deep Venous Thrombosis: A Case–Control Study’. Clinical Neurology and Neurosurgery 139 (2015): 66-69. Web. 15 Oct. 2015.

Uptodate.com,. ‘Aminocaproic Acid’. N.p., 2015. Web. 15 Oct. 2015.

Haldol for Agitation

BOLUS

  • 0.5-10mg initially, then q15-30 minutes until calm achieved (double initial bolus dose sequentially)
  • Maintenance dose: administer 25% of last bolus dose q6h, then taper over several dose
  • Monitor ECG and QTc
    • QTc prolongation with ≥35 mg/day
    • risk of torsade greater if ≥35 mg received within <6 hours

DRIP

  • Continuous infusions 0.5-2 mg/hour
  • may load with 2.5 mg IVx1