Urea for Hyponatremia

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

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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).

Foley On Arrival Flowchart

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