Tag: neurocritical care

Brain Death Checklist 2024

brain-death-checklistDownload

Greer DM, Kirschen MP, Lewis A, Gronseth GS, Rae-Grant A, Ashwal S, Babu MA, Bauer DF, Billinghurst L, Corey A, Partap S, Rubin MA, Shutter L, Takahashi C, Tasker RC, Varelas PN, Wijdicks E, Bennett A, Wessels SR, Halperin JJ. Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline. Neurology. 2023 Dec 12;101(24):1112-1132. doi: 10.1212/WNL.0000000000207740. Epub 2023 Oct 11. Erratum in: Neurology. 2024 Feb 13;102(3):e208108. PMID: 37821233; PMCID: PMC10791061.

Brain Death: metabolic confounders

REFERENCE:

Greer DM, Kirschen MP, Lewis A, Gronseth GS, Rae-Grant A, Ashwal S, Babu MA, Bauer DF, Billinghurst L, Corey A, Partap S, Rubin MA, Shutter L, Takahashi C, Tasker RC, Varelas PN, Wijdicks E, Bennett A, Wessels SR, Halperin JJ. Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline. Neurology. 2023 Dec 12;101(24):1112-1132. doi: 10.1212/WNL.0000000000207740. Epub 2023 Oct 11. Erratum in: Neurology. 2024 Feb 13;102(3):e208108. PMID: 37821233; PMCID: PMC10791061.

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LHH Cangrelor Guidelines

Cangrelor Dosing Guideline for  Emergency Stent Placement in Interventional Neuroradiology 

Background: 

In interventional cardiology, the loading dose for cangrelor has been 15-30 mcg/Kg, and maintenance dose has been 4 mcg/kg/min. This dose has been reduced in interventional neuroradiology (INR) procedures because of the higher risks of intracranial bleed.  This guideline presents recommendations for dosing and monitoring of cangrelor in INR procedures. 

Neurologic Indications: 

  1. Acute ischemic stroke with tandem occlusion requiring emergent carotid artery stenting 
  1. Acute ischemic stroke with intracranial stenosis requiring emergent stenting 
  1. Ruptured or unruptured intracranial aneurysm requiring bailout stenting 

PROTOCOL

Give cangrelor IV bolus and start cangrelor drip. 

    1. BOLUS: Give 7 mcg/Kg IV bolus, 2-5 minutes prior to stent placement. 
    1. MAINTENANCE DRIP: Start 1-2 mcg/Kg/min 30 seconds after bolus dose has been given. 
    1. NOTE:  No heparin is to be given during the neurointerventional procedure. 

    Check PRU 7-10 minutes after cangrelor drip has been started. 

      1. PRU goal should be specified by interventionalist. 
      1. If PRU is not at goal, adjust by 0.25 mcg/Kg/min, recheck PRU. 

      Maintain cangrelor drip x 2-6 hours. 

        Obtain non contrast head CT if needed to rule out hemorrhage.  

          Once maintenance drip is completed, switch to an oral agent. 

            Ticagrelor (preferred) 

              1. LOAD: Administer 180mg of ticagrelor (loading dose) at any time during cangrelor infusion or immediately after discontinuing cangrelor infusion 
              1. MAINTENANCE:  After loading dose, start maintenance dose of 60-90mg PO BID 

              Alternative agents: 

                1. Clopidogrel:   
                1. LOAD: Administer 600mg of clopidogrel immediately after discontinuing cangrelor infusion. 
                1. Do not administer clopidogrel prior to cangrelor discontinuation. 
                1. MAINTENANCE: After loading dose, start maintenance dose of 75mg once daily. 
                1. Prasugrel:  
                1. LOAD: Administer 60mg of prasugrel immediately after discontinuing cangrelor infusion. 
                1. Do not administer prasugrel prior to cangrelor discontinuation. 
                1. MAINTENANCE: After loading dose, start maintenance dose of 10mg once daily.   
                1. NOTE: Patients with history of TIA or stroke are associated with increased risk of fatal bleeding with the use of prasugrel.  Prasugrel is also not recommended in patients 75 years or older and patients <60 Kg.  Reduced dosing is available for patients <60Kg, but other agents as above are preferred.  

                Start aspirin 325 mg PO on day 1 followed by subsequent doses of 81mg PO daily, together with maintenance dose of oral P2Y12 inhibitor.   

                  1. NOTE: Maintenance doses of aspirin >100 mg daily reduce the effectiveness of ticagrelor and should be avoided.  This warning does not apply to clopidogrel or prasugrel.  

                  Obtain CT/CTA in a.m.  

                    References: 

                    1. Cagnazzo F, Radu RA, Derraz I, Lefevre PH, Dargazanli C, Machi P, Morganti R, Gascou G, Fendeleur J, Rapido F, Costalat V. Efficacy and safety of low dose intravenous cangrelor in a consecutive cohort of patients undergoing neuroendovascular procedures. J Neurointerv Surg. 2023 Mar 15:jnis-2023-020094. doi: 10.1136/jnis-2023-020094. Epub ahead of print. PMID: 36922032. 
                    1. Linfante I, Ravipati K, Starosciak AK, Reyes D, Dabus G. Intravenous cangrelor and oral ticagrelor as an alternative to clopidogrel in acute intervention. J Neurointerv Surg. 2021 Jan;13(1):30-32. doi: 10.1136/neurintsurg-2020-015841. Epub 2020 May 15. PMID: 32414891. 
                    1. Aguilar-Salinas P, Agnoletto GJ, Brasiliense LBC, Santos R, Granja MF, Gonsales D, Aghaebrahim A, Sauvageau E, Hanel RA. Safety and efficacy of cangrelor in acute stenting for the treatment of cerebrovascular pathology: preliminary experience in a single-center pilot study. J Neurointerv Surg. 2019 Apr;11(4):347-351. doi: 10.1136/neurintsurg-2018-014396. Epub 2018 Dec 14. PMID: 30552167. 
                    1. Cheddad El Aouni M, Magro E, Abdelrady M, Nonent M, Gentric JC, Ognard J. Safety and Efficacy of Cangrelor Among Three Antiplatelet Regimens During Stent-Assisted Endovascular Treatment of Unruptured Intracranial Aneurysm: A Single-Center Retrospective Study. Front Neurol. 2022 Mar 4;13:727026. doi: 10.3389/fneur.2022.727026. PMID: 35309565; PMCID: PMC8931395. 
                    1. Holden DN, Entezami P, Bush MC, Field NC, Paul AR, Boulos AS, Yamamoto J, Dalfino JC. Characterization of antiplatelet response to low-dose cangrelor utilizing platelet function testing in neuroendovascular patients. Pharmacotherapy. 2021 Oct;41(10):811-819. doi: 10.1002/phar.2619. Epub 2021 Sep 18. PMID: 34496076. 
                    1. Rodriguez‐Calienes, A., et al. Safety of Intravenous Cangrelor Versus Dual Oral Antiplatelet Loading Therapy in Endovascular Treatment of Tandem Lesions: An Observational Cohort Study. Stroke: Vascular and Interventional Neurology. 2023;0:e001020.  Oct 2023 doi.org/10.1161/SVIN.123.001020. 

                    CTP overestimates ischemic core

                    • Background and Purpose:
                    • Studies suggest CT perfusion (CTP) could overestimate ischemic core in early time frames.
                    • Aim to evaluate the influence of time and collateral status on ischemic core overestimation.
                    • Methods:
                    • Retrospective study on large-vessel stroke patients with reperfusion after endovascular treatment.
                    • Ischemic core and collateral status estimated on baseline CTP.
                    • Hypoperfusion intensity ratio used for collateral status assessment.
                    • Ischemic core overestimation defined when CTP-derived core > final infarct volume.
                    • Results:
                    • Analysis of 407 patients with median CTP-derived core of 7 mL and final infarct volume of 20 mL.
                    • Twenty percent exhibited ischemic core overestimation.
                    • Poor collateral status and earlier onset to imaging time independently associated with overestimation.
                    • Poor collateral status impact varied with onset to imaging time, stronger in early imaging patients.
                    • Conclusions:
                    • Poor collateral status may lead to higher ischemic core overestimation on CTP, especially in earlier time frames.
                    • CTP reflects hemodynamic state; consider collateral status and onset to imaging time when estimating core.

                    Take home:
                    This study underscores that poor collateral status significantly contributes to overestimating the ischemic core on CT perfusion (CTP), particularly in the early imaging window. CTP should be viewed as reflecting hemodynamic conditions rather than definitive tissue fate. Clinicians should be cautious in interpreting CTP results, considering collateral status and the time from symptom onset to imaging, as these factors play crucial roles in accurate ischemic core estimation.

                    García-Tornel Á, Campos D, Rubiera M, et al. Ischemic Core Overestimation on Computed Tomography Perfusion. Stroke. 2021;52(5):1751-1760. Accessed November 30, 2023.

                    CSF Tests Primer

                    Here are some of the tests that can be performed on the cerebrospinal fluid, and the indications for each test.

                    Basic Tests:

                    • CSF cell count 1
                    • CSF glucose
                    • CSF protein
                    • CSF chloride: not routine; abnormal when brain homeostasis is observed, nonspecific

                    Tests for Infectious Diseases (nonspecific):

                    • CSF culture with gram stain
                    • CSF fungal culture
                    • CSF Fungitell B-D Glucan: detects (1à3)-B-D-glucan (component of fungal cell wall), useful in detecting invasive fungal infections, s.a. Candida, Aspergillus, etc.; not specific to any particular type of fungus
                    • CSF Acid fast culture
                    • CSF lactate; lactic acid:  elevated in bacterial (but not viral) meningitis; also elevated in some metabolic / mitochondrial disordrees, ischemic stoke, certain brain tumors

                    Direct Bacterial, Fungal or Viral Antigen Testing:

                    • CSF PCR Panel (E. coli K1, H, influenza, Listeria monocytogenes, N. meningitidis, S. pneumoniae, S. agalactiae, CMV, enterovirus, HSV-1, HSV-2, HHV-6, human parechovirus, VZV, cryoptococcus neoformans/gatti)
                    • Bacterial
                      • CSF Lyme Ab
                      • CSF Borrelia burgdorferi IgG
                      • CSF VDRL Titer CSF
                    • Protozoa
                      • Toxoplasma gondii IgG/IgM
                      • CSF Remington toxo
                      • Fungal
                      • CSF cryptococcal antigen
                      • CSF Histoplasma Ag Immunoassay
                    • Viral
                      • CSF VZV Detection by PCR  
                      • CSF EBV detection PCR
                      • CSF herpes simples 1/2 PCR
                      • CSF JC Virus DNA by PCR
                      • CSF WNV IgG/IgM Ab; CSF WNV
                      • CSF CMV by PCR

                    Vasculitis:  [cell count and differential, cytology, IgG index, oligoclonal bands]

                    • CSF cultures to r/o infectious causes of vasculitis
                    • CSF PCR testing to detect presence of specific pathogens (e.g. HSV or VZV) which may cause vasculitis
                    • Cell count and differential [(+) WBC], Protein and glucose levels (abnormal indicates inflammation)
                    • CSF Cytology (atypical cells)
                    • CSF IgG Index  [measures intrathecal production of IgG, elevated in various inflammatory conditions, including some forms of vasculitis]; normal CSF IgG index is <0.7
                    • CSF oligoclonal band profile (IgG index); CSF protein electrophoresis includes CSF IgG index and oligoclonal bands [OCBs are often associated with inflammatory and demyelinating disorders of CNS (s.a. MS), not specific to vasculitis, but presence can contribute to overall diagnostic picture]
                    • Cytokine Analysis: measurement of specific cytokines (s.a. IL-6 or TNF-alpha), may provide insights into the inflammatory processes
                    • Flow Cytometry: analyzes cellular composition of CSF, abnormal cell populations that inflammatory or neoplastic process
                    • Myelin Basic Protein (MBP) and Tau Protein: Elevated levels suggest ongoing demyelination and neuronal damage which can occur in the setting of vasculitis.

                    *Note: Both the CSF IgG index and OCB profile provide information about the immune response within the central nervous system, but they focus on different aspects. The CSF IgG index measures the ratio of IgG in the CSF to IgG in the blood, indicating intrathecal IgG production. OCBs, on the other hand, are specific bands of immunoglobulins detected in the CSF, suggesting intrathecal synthesis of immunoglobulins.

                    Encephalitis:

                    • NMDA receptor Ab by CBA-IFA CSF RFx Titer:  detects Ab against NMDA receptors in the CSF
                      • NMDA receptors – glutamate receptor involved in transmission of signals between nerve cells
                      • Antibodies against NMDA receptors associated with anti-NMDA receptor encephalitis (autoimmune d/o, Ab produced against NMDA receptors, leading to inflammation in the brain)

                    Neoplastic:

                    • CSF Flow Cytometry: analyzes cellular composition of CSF for abnormal cell populations (indicating inflammatory or neoplastic process)
                    • CSF Cytology: (+) abnormal cells s.a. tumor cells
                    • CSF tumor markers:  AFP, B-HCG, Alpha-1-antitrypsin (elevated in germ cell tumors)
                    • CSF LDH: elevated levels nonspecific, may be associated with neoplastic process
                    • CSF ACE (Angiotensin Converting Enzyme): supports diagnosis of neurosarcoidosis, elevated levels indicate granulomatous inflammation, but nonspecific

                    Others:

                    • CSF Neuron specific enolase: marker for neuronal damage or injury, asses extent of neuronal damage, nonspecific; levels are increased in TBI, stroke, neurodegenerative disorders, some brain tumors
                    • MOG Antibody with reflex to titer CSF: MOG (myelin oligodendrocyte glycoprotein) antibody is associated with autoimmune demyelinating disease of CNS; MOG is a glycoprotein on the surface of myelin sheaths; this Ab is associated with MOG-Ab-associated-encephalomyelitis (MOG-EM), acute disseminated encephalomyelitis (ADEM), optic neuritis (ON) and transverse myelitis ™
                    • B2 Microglobulin CSF: B2 microglobulin is a component of MHC I molecules; present in various body fluids, including blood and CSF; CSF levels can be elevated in conditions involving disruption of BBB and immune system activation within the CNS; not part of routine CSF analysis; can measure levels in multiple myeloma and leptomeningeal involvement, HIV-associated neurological disorders, lymphomas or lymphoproliferative disorders involving CNS
                    • CSF Adenosine deaminase: ADA enzyme involved in breakdown of adenosine; used as part of diagnostic work-up for TB meningitis; nonspecific may be elevated also in other infectious conditions including viral and fungal infections
                    • Alzheimers Disease Eval, CSF:  CSF biomarker analysis can support clinical diagnosis, but is used in conjunction with other assessments; CSF testing is usually employed in research settings and includes beta-amyloid 42, total tau, phosphorylated tau, AB42/AB40 ratio, neurofilament light and YKL-40
                    • CSF 14-3-3 Protein Tau:  studied as a potential biomarker for Creutzfeldt-Jakob disease; microtubule-associated proteins abundant in neurons; can become abnormally phosphorylated and aggregate in certain neurodegenerative disorders, s.a. Alzheimer’s disease, forming neurofibrillary tangles;
                    • CSF amino acids: not routine, consider if metabolic or neurological disorders suspected s.a. inborn errors of metabolism, aminoacidopathies, some neurodegenerative disorders

                    Management of Hiccups in Neurocritical Care

                    Hiccup Reflex Arc:

                    Activation of “hiccup center” by lesions in the CNS or periphery triggers hiccups mediated via phrenic and intercostal nerves, leading to myoclonic repetitive contractions of the diaphragm and accessory muscles. The characteristic “hic” sound is produced due to reflex closure of the glottis via recurrent laryngeal nerve.

                    Stepwise management protocol

                    • mostly based on observational reports and case series, and clear-cut guidelines are lacking
                    • majority of the cases, no cause is found and the treatment is mainly empirical to ameliorate the symptoms

                    Anecdotal and nonpharmacological treatment methods:

                    Pharmacological Treatment:

                    REFERENCE:

                    Rajagopalan, V. et al. (2021) ‘Hiccups in neurocritical care’, Journal of Neurocritical Care, 14(1), pp. 18–28. doi:10.18700/jnc.200018.

                    Urea for Hyponatremia

                    need systematic review on use of urea specifically in NCC, for treatment of cerebral edema, ICP crises, hyponatremia, cerebral salt wasting

                    ==========================

                    DOSAGE:

                    SIADH-associated hyponatremia

                    • Goal of initial Tx: 24h Na increase by 4 to 6 mEq/L (max: 8 mEq/L in 24h)
                    • if symptomatic (acute or chronic), increase Na by 4 to 6 mEq/L within first 6h, then maintain Na for 24h
                    • Initial: 15 to 30 g daily in 1 or 2 divided doses; titrate dose based on clinical response in increments of 15 g at weekly intervals; maximum daily dose: 60 g/day

                    MECHANISM OF ACTION:

                    • normalizes sodium by inducing osmotic excretion of free water
                    • ameliorates hyponatremia in SIADH secretion by a more specific effect, diminishing the natriuresis in association with increased medullary urea content

                    Sample Case: Urea 30g (500 mosmol) given to a 50Kg woman with 25L body water [Na 120 mmol/L, UOsm 500 mosmol/L]

                    urea rapidly enters muscle cells, distributing in total body water –> increase in plasma osmolality by 20-mosmol increase in plasma osmolality, no expansion of ECF volume

                    urea is slow to cross the blood–brain barrier (reflection coefficient of 0.5)

                    10-mosmol osmotic gradient from plasma to brain is created –> draws water out of the brain

                    Over time, urea gradient across BBB diminishes

                    (1) slow diffusion of urea into the brain

                    (2) loss of urea from the plasma caused by urea excretion in the urine.

                    Beginning immediately, urea is excreted in the urine (with normal renal function, all is excreted within 12h) –> loss of 1L water (electrolyte free) –> decrease in plasma urea –> decrease is plasma osmolality, increases serum sodium by 5 mEq/L, preventing water from re-entering brain

                    REFERENCES:

                    Sterns, R.H., Silver, S.M. and Hix, J.K. (2015) ‘Urea for hyponatremia?’, Kidney International, 87(2), pp. 268–270. doi:10.1038/ki.2014.320.

                    Urea (systemic): Drug information (no date) UpToDate. Available at: https://www.uptodate.com/contents/urea-systemic-drug-information?search=urea&source=panel_search_result&selectedTitle=1~147&usage_type=panel&showDrugLabel=true&display_rank=1 (Accessed: 20 August 2023).

                    Antimicrobial Prophylaxis in Neurosurgery

                    From UpToDate:

                    Choose vancomycin if:

                    1. MRSA/S. epidermidis frequent cause in your hospital
                    2. Previously colonized with MRSA
                    3. Allergic to PCN / cephalosporins

                    Give first dose within 60 minutes before procedure (60-120minutes for vancomycin)

                    Redose during OR if:

                    1. procedure >3hours
                    2. major blood loss
                    3. extensive burns

                    Redose after OR?

                    1. Readministration of antimicrobial prophylaxis following closure of surgical incision is not warranted for clean and clean-contaminated procedures, even in the presence of a drain
                    2. In general, repeat antimicrobial dosing following wound closure is not necessary and may cause patient harm (increased risk of antimicrobial resistance and C. difficile infection)
                    3. If prophylaxis continued after OR, duration should not exceed 24h.

                    From Northwell Policies & Procedures:

                    1. Vancomycin prophylaxis should be considered for patients with known MRSA colonization or at high risk for MRSA colonization in the absence of surveillance data (e.g., patients with recent hospitalization, nursing-home residents, hemodialysis patients).
                    2. A single dose of gentamicin for surgical prophylaxis based on the patient’s weight can be given safely (dosing recommendations provided).
                    3. Routine use of antimicrobial irrigation solutions during surgery is not recommended.
                    4. For patients already receiving antimicrobials prior to surgery, it is unnecessary to administer additional antimicrobials for surgical prophylaxis provided that the current regimen is appropriate in spectrum for the surgery planned and timing of administration of the current antimicrobial regimen is appropriate relative to incision time.
                    5. Administration must occur no more than 60 minutes prior to incision (except for vancomycin and fluoroquinolones where a 120 minute period is allowed). Antibiotic infusions should ideally be completed prior to incision.
                    6. Intra-operative re-dosing is strongly recommended to ensure adequate serum and tissue concentrations of the antimicrobial if the duration of the procedure exceeds two half-lives of the drug or there is excessive blood loss during the procedure. This roughly corresponds with re-dosing antimicrobials at a frequency of one interval shorter than usual.
                    7. Additional intra-operative doses may not be warranted in patients for whom the half-life of the antimicrobial is prolonged, such as adult patients with renal insufficiency
                    8. In patients receiving post-operative antibiotic therapy, post-operative dosing should be timed from the time last dose given during surgery.
                    9. For clean or clean-contaminated procedures, 2017 CDC guidelines recommend not to administer additional prophylactic antimicrobial doses after the surgical incision is closed in the operating room, even in the presence of a drain (reference 2). Based on this recommendation, these guidelines recommend to limit post-operative antibiotics as much as possible and if post-operative antibiotics are given, should be discontinued within 24 hours after surgery time. For cardiac procedures, no longer than 48 hours
                    10. The use of antimicrobial agents for dirty procedures (class III or IV) or established infections is classified as treatment of presumed infection, not prophylaxis. Such a patient requires documentation within their medical record at the time of the procedure to clarify the reason for the selected antibiotic (i.e. active or presumed infection).
                    11. Post-operative cefazolin should be dosed at maximum dose of 2g q8h (i.e. 3g should not be used).

                    REFERENCE:

                    UpToDate. Available at: https://www.uptodate.com/contents/antimicrobial-prophylaxis-for-prevention-of-surgical-site-infection-in-adults?search=surgical+antibiotic+prophylaxis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H188863 (Accessed: 08 August 2023).

                    System Policy & Procedure Manual: Antibiotic Prophylaxis in Surgery PHT.476. approved 04/18/2023. Northwell Health