IV Diclofenac Sodium for Central Fever

Dose:

  • initial bolus: 0.2 mg/kg in 100 ml of saline solution over 30 minutes
  • continuous infusion:
    • 75 mg in 50 ml NS
    • dosage 0.004–0.08mg/kg/hour titrated to body temperature
    • discontinued if temperature <37.5°C for more than 12 hours on a dose of 0.004 mg/kg/hour
  • Monitor BP, CBC, liver and kidney function
  • continuous monitoring of temperature with esophageal probe

Side effects: hypotension, reduced MAP. oliguria, reduced HR, CPP, PBtO2

Table. Studies on use of diclofenac in the ICU

Diclofenac sodium low dose IV infusion is not commonly used in the ICU for the treatment of central fever. Needs further studies and clinical experience. This method / dosing schedule is lifted from a case report on the successful treatment of central fever in a stroke patient. (reference below)

Reference:

Giaccari, L., Pace, M., Passavanti, M., Sansone, P., Esposito, V., Aurilio, C., & Pota, V. (2019). Continuous intravenous low-dose diclofenac sodium to control a central fever after ischemic stroke in the intensive care unit: a case report and review of the literature. Journal Of Medical Case Reports13(1). doi: 10.1186/s13256-019-2281-7

Hemorrhagic Transformation in Stroke – Predictive Scores

Published predictive scores of hemorrhagic transformations

  • HTI: Hemorrhagic Transformation Index Score
  • ASPECTS: Alberta Stroke Program Early CT Score
  • iScore: Ischemic Stroke Predictive Risk Score
  • HAT: hemorrhage after thrombolysis
  • HeRS: Hemorrhage Risk Stratification Score
  • SEDAN: Blood Sugar [glucose] on admission, Early infarct signs and [hyper] Dense cerebral artery sign on admission computed tomography [CT] head scan, Age, and NIHSS
  • SITS- SICH: Safe Implementation of Treatments in Stroke (SITS) Symptomatic Intracerebral Hemorrhage Risk Score
  • GRASPS: Get With The Guidelines–Stroke symptomatic intracerebral hemorrhage risk
  • MSS: Multicenter rt-PA Stroke Survey Group Score
  • SPAN-100: Stroke Prognostication using Age and NIH Stroke Scale

Summary of predictors of hemorrhagic transformation.

Reference:

ANDRADE, J., MOHR, J., LIMA, F., BARROS, L., NEPOMUCENO, C., PORTELA, L., & SILVA, G. (2020). Predictors of hemorrhagic transformation after acute ischemic stroke based on the experts’ opinion. Arquivos De Neuro-Psiquiatria78(7), 390-396. doi: 10.1590/0004-282×20200008

Glibenclamide for Brain Edema

PATHOPHYSIOLOGY OF CEREBRAL EDEMA IN STROKE:

  • Following ischemic insult, SUR1-TRPM4 ion channel expressed in all cells of the neurovascular unit.
  • Early stages of ischemia, channel upregulation occurs at the luminal and abluminal surfaces of the vascular endothelium, mediating an ionic gradient from the intraluminal space to the interstitial space.
  • Water transported from vasculature into the parenchyma.
  • Formation of ionic gradient followed by or accompanied by breakdown of the BBB.
  • Capillary structure is maintained, preventing extravasated of cells, while vasculature becomes open to water movement and movement of macromolecules s.a. Immunoglobulin / albumin.
  • Opening facilitates osmotic and hydrostatic movement of water into brain.
  • Tight junctions between vascular endothelial cells degraded by MMP9, which further facilitates fluid movement into the brain.

MECHANISM OF ACTION OF GLIBENCLAMIDE

  • Glibenclamide is an anti-edema drug.
  • Glibenclamide blocks the activity of the SUR1-TRPM4 ion channel.
  • This channel is upregulated in the CNS only after ischemia / trauma.
  • Glibenclamide blocks this cascade, protects the neurovascular unit.
  • First impact is on the capillary endothelium, rather than neurons.
  • Glibenclamide does not cross the uninjured BBB, only the channels up-regulated in the vascular endothelium are relevant until such time as the BBB is disrupted.

Reference:

Jacobson, S., MacAllister, T. and Geliebter, D., 2020. Found in translation: The rationale behind the early development of glibenclamide in large hemispheric infarction. Neuroscience Letters, 716, p.134672.

Atrial Fibrillation: anticoagulate or not?

Interesting analysis from Annals of Internal Medicine.  The decision to start anticoagulation in atrial fibrillation, using CHADSVASC score is not so clear cut.  See tables below.

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Reference:

Shah, S., Eckman, M., Aspberg, S., Go, A. and Singer, D. (2018). Effect of Variation in Published Stroke Rates on the Net Clinical Benefit of Anticoagulation for Atrial Fibrillation. Annals of Internal Medicine.

TIA Management

Low-risk TIA

  • ABCD scores 0-3
  • out patient work-up in the next 1-2 days
  • alternative is to admit
  • begin ASA 81mg or plavix 75 or ASA 25/ER dipyridamole 200mg BID
  • perform carotid imaging: US, CTA, MRA
  • consider TTE (if bilateral infarcts on CT, high suspicion of cardioembolic source and TTE normal – obtain TEE)
  • consider 30d ambulatory cardiac monitor to document cryptogenic Afib
  • smoking cessation
  • Statins:
    • start high-dose statin (atorvastatin 40-80; rosuvastatin 20-40)
    • consider mod intensity statin if >75 y/o (atorvastatin 10-20, rosuvastatin 5-10, simvastatin 20-40, pravastatin 40-80)
  • consider anticoagulation if ECG (+) Afib, calculate CHADS or CHADSVASC and HAS-BLED scores
  • ? Referral to vascular neurologist or cardiologist

 

High-Risk TIA:

  • admit
  • permissive HTN
  • gradually lower BP limits over 24-48h

 

 

Reference:

Gross, H. and Grose, N. (2017). Emergency Neurological Life Support: Acute Ischemic Stroke. Neurocritical Care, 27(S1), pp.102-115.

Criteria for Thrombectomy / Endovascular Treatment of Stroke

Patients eligible for intravenous alteplase should receive intravenous alteplase even if endovascular treatments are being considered

Patients should receive endovascular therapy with a stent retriever if they meet all the following criteria:

  1. prestroke mRS score 0–1,
  2. acute ischemic stroke receiving intravenous alteplase within 4.5 h of onset
  3. causative occlusion of the internal carotid artery or proximal MCA (M1),
  4. age >18 years, (note: there is no upper age limit),
  5. NIHSS score of C6,
  6. ASPECTS of C6
  7. treatment can be initiated (groin puncture) within 6 h of symptom onset

As with intravenous alteplase, reduced time from symptom onset to reperfusion with endovascular therapies is highly associated with better clinical outcomes

When treatment is initiated beyond 6 h from symptom onset, the effectiveness of endovascular therapy is uncertain for patients with acute ischemic stroke who havecausative occlusion of the internal carotid artery or proximal MCA (M1)

In carefully selected patients with anterior circulation occlusion who have contraindications to intravenous alteplase, endovascular therapy with stent retrievers completed within 6 h of stroke onset is reasonable

Although the benefits are uncertain, use of endovascular therapy with stent retrievers may be reasonable for carefully selected patients with acute ischemic stroke in whom treatment can be initiated (groin puncture) within 6 h of symptom onset and who have causative occlusion of the M2 or M3 portion of the MCAs, anterior cerebral arteries, vertebral arteries, basilar artery, or posterior cerebral arteries

Endovascular therapy with stent retrievers may be reasonable for some patients <18 years of age with acute ischemic stroke who have demonstrated large vessel occlusion in whom treatment can be initiated (groin puncture) within 6 h of symptom onset, but the benefits are not established in this age group

Observing patients after intravenous alteplase to assess for clinical response before pursuing endovascular therapy is not required to achieve beneficial outcomes and is not recommended

Endovascular therapy with stent retrievers is recommended over intra-arterial fibrinolysis as first-line therapy

It might be reasonable to favor conscious sedation over general anesthesia during endovascular therapy for acute ischemic stroke. However, the ultimate selection of anesthetic technique during endovascular therapy for acute ischemic stroke should be individualized based on patient risk factors, tolerance of the procedure, and other clinical characteristics

Reference:

Gross, H. and Grose, N. (2017). Emergency Neurological Life Support: Acute Ischemic Stroke. Neurocritical Care, 27(S1), pp.102-115.

Checklist: Bleed post TPA

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Half life of TPA is ~5 minutes and only 20% is present and active 10 mins after completion of infusion, but PT and PTT prolongation and fibrinogen levels are decreased x 24 hours or more.

Checklist:

  • STOP alteplase
  • VS q15h, GCS, pupil response, treat BP, increased ICP
  • Neurosurgery consult
  • DIAGNOSTICS: STAT CT head, PT/PTT, platelets, fibrinogen, type and cross 2-4 unit pRBC
  • THERAPEUTICS:
  1. Transfuse cryoprecipitate 6-8 units IV
    1. If fibrinogen 50-100mg/dL transfuse 10 bags
    1. If fibrinogen <50 mg/dL transfuse 20 bags
  2. Check fibrinogen level 30-60 mins post transfusion, goal fibrinogen level >100 mg/dL
  3. ALTERNATIVE: transfuse single donor platelets or 6-8 bags of random donor platelets

*each bag of cryoprecipitate contains 200-250 mg of fibrinogen, increases fibrinogen levels by 6-8 mg/dL (in a 70 Kg adult)

*half life of fibrinogen is 3-5 days

Reference:

Gross, H. and Grose, N. (2017). Emergency Neurological Life Support: Acute Ischemic Stroke. Neurocritical Care, 27(S1), pp.102-115.

Abciximab for Reocclusion after tPA

Platelet-mediated thrombotic mechanisms may play a key role in rethrombosis after tPA lysis.  Rersidual thrombus provides a nidus for rethrombosis.  vWF is activated, which mediates platelet adhesion and formation of thrombus.

A thrombus which is platelet-rich can be dissolved rapidly by abciximub.  Abciximab-induced disaggregation of preformed platelet-rich thrombus is time-dependent.

In a prospective study, 4 patients with reocclusion after tPA clot lysis were treated with abciximab.  a 0.2mg/Kg bolus was given, followed by a maintenance infusion of 0.125 ug/kg/min x 12 hours.  

Dose for abciximab in UpToDate (for PCI):

Percutaneous coronary intervention (PCI): IV: 0.25 mg/kg bolus administered 10 to 60 minutes prior to start of PCI followed by an infusion of 0.125 mcg/kg/minute (maximum: 10 mcg/minute) for 12 hours

Reference:

Heo, J., Lee, K., Kim, S. and Kim, D. (2003). Immediate reocclusion following a successful thrombolysis in acute stroke: A pilot study. Neurology, 60(10), pp.1684-1687.

Uptodate. Abciximab: Drug information. Accessed 09/11/2017.

ABCD2 Score

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Table: ABCD2 Score

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TIA Prognosis and Key Mx Considerations by National Stroke Association

ABCD2 Score:

  • Discharge low risk scores (ABCD 0-3)
    • outpatient work-up within 1-2 days (alternate option: admit for work-up)
    • DIAGNOSTICS:
      • carotid imaging (US, CTA, MRA)
      • Consider TTE; if high suspicion for cardioembolic source / bilateral infarcts, obtain TEE
      • Consider 30-d ambulatory cardiac monitor to detect cryptogenic Afib
    • smoking cessation
    • THERAPEUTICS:
      • Start antiplatelet therapy:
        • ASA 81mg/day or
        • Clopidogrel 75mg/day or
        • ASA 25mg/ER dipyridamole 200mg BID
      • start high-intensity statins
        • Atorvastatin 40-80mg/d or
        • Rosuvastatin 20-40mg/day
      • *consider moderate intensity statins if >75y/o
        • Atorvastatin 10-20mg/d or
        • Rosuvastatin 5-10mg/d or
        • Simvastatin 20-40mg/d or
        • Pravastatin 40-80mg/d
      • Consider OAC or LMWH if rhythm shows atrial fibrillation – calculate CHADSVASC and HAS BLED score to guide therapy

    Admit high risk TIAs (ABCD2 scores >3)

    • Admit to hospital
    • Permissive hypertension (up to 220/120mm Hg) and gradually lower over 24-48h

Reference:

Stroke.org. (2017). [online] Available at: http://www.stroke.org/sites/default/files/resources/tia-abcd2-tool.pdf?docID [Accessed 31 Jul. 2017].

Gross, Hartmut, and Noah Grose. 2017. “Emergency Neurological Life Support: Acute Ischemic Stroke”. Neurocritical Care 27 (S1): 102-115. doi:10.1007/s12028-017-0449-9.