Tag Archives: nephrology

A New Algorithm to Differentiate Salt-wasting Syndrome from SIADH

In cerebral salt-wasting (CSW), natriuretic factor is produced in response to a central insult.  Natriuretic factor decreases sodium transport in proximal renal tubule which leads to urinary loss of sodium (and water) and depletion of extracellular volume.  Hypovolemia then triggers secretion of ADH, renin and aldosterone, which provides a negative feedback to decrease secretion of natriuretic factor.

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Differentiating CSW from syndrome of inappropriate antidiuretic hormone (SIADH) is problematic, laboratory work-up (urine and plasma sodium levels and urine and plasma osmolarity) is similar in both conditions.  CSW patients are usually volume depleted while SIADH patients are euvolemic.  The traditional approach of examining patient clinically to to determine volume status is inaccurate.

An interesting paper published in 2014 suggested a new algorithm to differentiate SIADH from CSW based on the effect of sodium correction on the fractional excretion of urate (FEUa).  FEurate is calculate using the folllowing formula:

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Expanded:

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Another formula:

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Normal FEUa = 4-11%, SIADH & CSW FEUa = >11%.  FEUa determines the percent excertion of the filtered load of urate at the glomerulus.

In SIADH, FEUa normalizes after correction of hyponatremia (see graph below):

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whereas in CSW, FEUa remains elevated >11% after correction of hyponatremia.  The reason is probably because natriuretic factor also decreases urate transport in the proximal tubule.

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Based on this finding, the paper suggests a new algorithm for determining the etiology of hyponatremia that omits reliance of UNa (and also plasma renin, aldosterone, atrial or brain antriuretic peptide, BUN/creatinine ratio).

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Based on this algorithm, a patient with hyponatremia should undergo correction of sodium by any means (water restriction or isotonic / hypertonic saline). Observing whether FEUa normalizes or remains increased would differentiate SIADH from CSW syndrome.

 

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Reference:

Maesaka, J., Imbriano, L., Mattana, J., Gallagher, D., Bade, N. and Sharif, S. (2014). Differentiating SIADH from Cerebral/Renal Salt Wasting: Failure of the Volume Approach and Need for a New Approach to Hyponatremia. Journal of Clinical Medicine, 3(4), pp.1373-1385.

 

 

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Classification and Severity of Diabetes Insipidus

Interesting classification of DI, taken from Neurology India, groups DI into mild and severe based on some clinical and lab findings.

 

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This was their protocol for diagnosis and management of DI in patients who underwent craniopharyngioma surgery.

 

Protocol for diabetes insipidus

  • Diagnosis:  UO > 4ml/kg/h over 6 h perior OR Na >145 mEq/L with USG <1.005
  • Monitoring
    • if drowsy, unable to drink – measure Is and Os hourly, sum every 6 hours
    • Foley until UO reasonably controlled
    • intraop Na if surgery >6h determines type of IV fluids and if pitressin required in OR
    • measure Na q6h day 1
    • measure Na q12h day 2 until stable x 3 days
    • measure Na daily x 1 week
  • Treatment
    • Fluids until patient is awake and demonstrates intact thirst mechanism
      • 0.45% saline when UO 4-6 ml/Kg/h
      • D5W when UO >6ml/kg/h
    • DDAVP
      • day 1 – 5 unit IV boluses of pitressin
      • started as early as possible, usually on 2nd day, oral DDAVP 100 ug tablets of fractions of tablets
  • Adequacy of control
    • based on serum Na rather than Is and Os
      • check frequency >150 or <130 or inc/dec by >10mEg/L in 1 day

 

Other pearls:

  • Adipsia may be complication of hypothalamic damage
    • diminished thirst sensation
    • higher risk of developing hpyernatremia
    • require round the clock DDAVP
    • need to be trained to drink 2-3L water per day
    • gradually resolves with partial or complete thirst recovery by 9 months
  • Polydipsic with high UO
    • patient compensating with increased PO intake, normal or low Na
    • at risk for water intoxication or hyponatremia
    • use oral rehydration solution rather than plain water

 

Reference:

Chacko, AriG et al. “Evaluation Of A Protocol-Based Treatment Strategy For Postoperative Diabetes Insipidus In Craniopharyngioma”. Neurology India 63.5 (2015): 712.

Decompressive Hemicraniectomy,

Evidence for DHC:

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Mortality Reduction in Percentages:

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Mortality at 12months after malignant MCA infarction. Forest plot presenting risk difference and 95% confidence interval (CI) for a pooled analysis of mortality at 12months from RCTs comparing DC and best medical care:

Surgical Technique:

  • Place head in rigid 3-pin fixation
  • A large reverse question mark flap is turned to allow access to a large part of the hemicranium.
  • Large craniectomy of frontotemporoparietal region
  • Avoid frontal air sinus
  • Take the inferior bone cut as low as possible to the floor of the middle fossa and ronguer/drill additional bone to accomplish this
  • typical craniectomy flap measures at least 15 cm anteroposteriorly and 10 to 12 cm craniocaudal
  • dura is opened in a C-shaped or stellate manner
  • When the anterior temporal lobe is infarcted and tentorial herniation is present or impending, perform an anterior temporal lobectomy with resection of the uncus and visualization of the tentorial edge, third nerve, and midbrain
  • lax duraplasty with autologous pericranial graft, closure must be capacious; be able to pick up and freely slide the lax dural sac
  • Muscle reapproximated loosely or not at all
  • Scalp is closed in layers (drains optional but preferred)
  • parenchymal or subdural ICP monitor optional
  • bone flap typically discarded (prefer delayed cranioplasty with a custom implant) or store bone flap in abdominal wall or cryopreserve
  • transfer to NSICU without extubation.
Post-op Management:
  • standard ICU ICP management
  • attempt early extubation without gagging
  • early enteral nutrition by POD1
  • SQH after 24 hours unless with C/I
  • early trach / PEG if needed
  • if stable post-op CT, ASA after 24 h
  • aggressive PT, speech, rehab

 

While technical details certainly vary between individual surgeons or centers, this brief outline describes a typical operation: the procedure is performed in a supine position with the head rotated to the contralateral side. A wide curved incision is performed either beginning behind or in front of the ear. The scalp flap and temporalis muscle are then deflected to expose the skull. Burr holes are created and subsequently connected to achieve an anterior to posterior diameter of the craniectomy area of at least 12 cm, with the recommended diameter in adult TBI

patients being 15 cm. The DC is finally extended to expose the floor of the middle cranial fossa. An adequately sized craniectomy is essential in achieving the desired decompressive effect. Moreover, a suboptimal DC will lead to exacerbated external brain her niation and shear forces at the bone edges, which can cause intraparenchymal hemorrhage and kinking of the cerebral

veins. After sufficient bony decompression has been achieved, the dura is incised to create a large dural opening. For coverage of the exposed brain, allogenic or autologous dural grafts can be used.

Complications:

  • Hygroma / subdural fluid collection most common (50-58%), most clinically insignificant
  • delayed HCP in 7-12%
  • infection 2-7%
  • sinking flap syndrome (syndrome of trephined)

 

Operative technique of supratentorial DC. Artist’s rendition of a human head with a typical incision line for DC (gray line).

3D reconstruction of a human skull demonstrating burr holes (gray circles), craniectomy (gray area), and additional osteoclastic decompression of the middle cranial fossa floor (hatched area) as well as typical dural incision (red lines).

3D reconstruction of a human skull with a typical hemicraniectomy skull defect:

Intraoperative photography of a human brain after DC:

stepwise reduction in ICP after decompressive hemicraniectomy:

Suboccipital or Infratentorial Decompressive Craniectomy

In comparison with supratentorial DC, the technical details of suboccipital or infratentorial DC are less clearly established. Important aspects such as overall craniectomy size, laterality of the decompression, and necessity of resection of the posterior arch of the atlas all vary in the published literature. However, the basic surgical aim is decompression above the swollen cerebellum. In general, this procedure is performed with the patient in a prone or semi-prone/lateral position. A linear midline incision is made from the inion to the upper cervical spine, and the muscular layers are subsequently separated in the midline avascular plane, exposing the suboccipital skull, atlanto-occipital membrane, and posterior arch of the atlas. A wide craniectomy is performed extending into the foramen magnum. As the next step, to avoid tonsillar herniation, we routinely remove the posterior arch of the atlas. The dura is then usually opened in a Y-shaped fashion, and an expansion duroplasty is performed.

2018 AHA ASA Guidelines:

The guideline recommends early transfer of patients at risk of malignant cerebral edema to a center with neurosurgical expertise. Patient-centered preferences in shared decision-making regarding the interventions and limitations of care should be ascertained at an early stage. With regard to neurosurgical management, the guideline states that in patients ≤ 60 years of age, who deteriorate neurologically (defined as a decrease in the level of consciousness attributed to brain swelling despite medical therapy) within 48 h after MCA infarction, DC with expansion duroplasty is reasonable. In patients > 60 years of age, the same approach may be considered. For patients with cerebellar malignant stroke, the guideline recommends sub-occipital DC with expansion duroplasty upon neurological deterioration despite medical therapy, with concurrent EVD insertion to treat obstructive hydrocephalus.

Reference:

Gupta, Aman et al. “Hemicraniectomy For Ischemic And Hemorrhagic Stroke”. Neurosurgery Clinics of North America 28.3 (2017): 349-360.

Beez, T., Munoz-Bendix, C., Steiger, H. and Beseoglu, K. (2019). Decompressive craniectomy for acute ischemic stroke. Critical Care, 23(1).

Algorithm to Identify MRI Sequences

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<click here for MS Powerpoint file>

Reference:

“Introduction To Imaging: What Am I Looking At?”. YouTube. N.p., 2016. Web. 19 Dec. 2016.

 

 

Treatment of Aneurysms

  • Clipping Most aneurysms
  • Coiling Most aneurysms
  • Flow diversion Large proximal ICA aneurysms, blister aneurysms
  • Flow diversion with adjunctive coiling Large and giant aneurysms with wide necks
  • Intrasaccular flow diversion Bifurcation aneurysms with neck ≥4 mm
  • Coiling with assistive stenting Wide-neck aneurysms and aneurysms with branch vessels near/incorporating aneurysm neck
  • Parent vessel sacrifice or branch vessel sacrifice with bypass Dissecting aneurysms, giant aneurysms with branch vessels incorporating aneurysm neck
  • Parent vessel sacrifice without bypass Distal PICA aneurysms, distal PCA aneurysms, distal mycotic aneurysms

 

Reference:

Walcott, Brian P. et al. “Blood Flow Diversion As A Primary Treatment Method For Ruptured Brain Aneurysms—Concerns, Controversy, And Future Directions”. Neurocritical Care (2016): pp 1-9.

AEDs in Renal Failure / Hemodialysis

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How does renal disease affect AED levels?

  • Renal insufficiency alters the pharmacokinetics of seizure medications that are metabolized by the kidneyes, leading to increased half-lives and accumulation of the drug.
  • Albuminuria and acidosis that frequently occur in renal failure also decreases drug binding, increasing the free levels of AEDs and volume of distribution.
  • Gastroparesis delays maximum serum levels of AEDs, intestinal edema diminishes absorption of AEDs.

Take home message:  It is difficult to predict drug levels based on the creatinine clearance.

AEDs that are extensively eliminated by kidneys:

  • hydrosoluble
  • low molecular weight
  • low Vd
  • little protein-bound
  • Examples:  gapabentin, topiramate, ethosuxamide, vigabatrin, levetiracetam
  • accumulate in renal disease
  • easily removed by hemodialysis and requires post-HD administration

AEDs that are not extensively eliminated by kidneys:

  • lipophylic
  • high protein-bound
  • Examples:  carbamazepine, phenytoin, lamotrigine, benzodiazepines, valproate
  • little affected by renal disease
  • HD has little impact on carbamazepine, phenytoin and valproate levels
  • HD has unpredictable effects on benzodiazepines or oxcarbazepine monohidroxi derivative
  • 4-hour HD decreases lamotrigine levels by ~20%

Peritoneal dialysis has variable effects on AED serum levels, check free levels for drug adjustment

LEVETIRACETAM:

  • CrCl >80 mL/minute/1.73 m2: 500 to 1,500 mg every 12 hours
  • CrCl 50 to 80 mL/minute/1.73 m2: 500 to 1,000 mg every 12 hours
  • CrCl 30 to 50 mL/minute/1.73 m2: 250 to 750 mg every 12 hours
  • CrCl <30 mL/minute/1.73 m2: 250 to 500 mg every 12 hours
  • End-stage renal disease (ESRD) requiring hemodialysis: Dialyzable (50%); 500 to 1,000 mg every 24 hours; supplemental dose of 250 to 500 mg is recommended posthemodialysis
  • Peritoneal dialysis (PD): 500 to 1,000 mg every 24 hours (Aronoff 2007)
  • Continuous renal replacement therapy (CRRT): 250 to 750 mg every 12 hours (Aronoff 2007)

PHENYTOIN:

  • There are no dosage adjustments provided in the manufacturer’s labeling; <5% excreted as unchanged drug. Serum concentration may be difficult to interpret in renal failure. Monitoring of free (unbound) concentrations or adjustment to allow interpretation is recommended.
  • Fosphenytoin:  There are no dosage adjustments provided in the manufacturer’s labeling. Free (unbound) phenytoin levels should be monitored closely in patients with renal disease or in those with hypoalbuminemia; furthermore, fosphenytoin clearance to phenytoin may be increased without a similar increase in phenytoin clearance in these patients leading to increase frequency and severity of adverse events.

CARBAMAZEPINE:

  • Dosage adjustments are not required or recommended in the manufacturer’s labeling; however, the following guidelines have been used by some clinicians:
  • Children and Adults:
    • GFR <10 mL/minute: Administer 75% of dose
    • Hemodialysis, peritoneal dialysis: Administer 75% of dose (postdialysis)
  • Continuous renal replacement therapy (CRRT):
    • Adults: No dosage adjustment recommended
    • Children: Administer 75% of dose

PHENOBARBITAL

  • There are no specific dosage adjustments provided in the manufacturer’s labeling; reduced doses are recommended.
  • The following guidelines have been used by some clinicians:
    • CrCl ≥10 mL/minute: No dosage adjustment necessary.
    • CrCl <10 mL/minute: Administer every 12 to 16 hours.
    • HD (moderately dialyzable [20% to 50%]): Administer dose before dialysis and 50% of dose after dialysis.
    • PD:  Administer 50% of normal dose.
    • CRRT: Administer normal dose and monitor levels.

VALPROIC ACID:

  • Mild to severe impairment: No dosage adjustment necessary (including patients on hemodialysis); however, due to decreased protein binding in renal impairment, monitoring only total valproate concentrations may be misleading.

 

LORAZEPAM:

  • Dosing: Renal Impairment
  • Oral: No dosage adjustment necessary
  • IM, IV: Risk of propylene glycol toxicity. Monitor closely if using for prolonged periods of time or at high doses.
    • Mild-to-moderate disease: Use with caution.
    • Severe disease or failure: Use is not recommended.

MIDAZOLAM:

  • Dosing: Renal Impairment
    • There are no dosage adjustments provided in manufacturer’s labeling; however, patients with renal failure receiving a continuous infusion cannot adequately eliminate the active hydroxylated metabolites (eg, 1-hydroxymidazolam) contributing to prolonged sedation sometimes for days after discontinuation
  • Intermittent HD:  Supplemental dose not necessary
  • CVVH: Unconjugated 1-hydroxymidazolam not effectively removed; 1-hydroxymidazolamglucuronide effectively removed; sieving coefficient = 0.45
  • PD: Significant drug removal unlikely

LAMOTRIGINE:

  • There are no dosage adjustments provided in the manufacturer’s labeling. Decreased maintenance dosage may be effective in patients with significant renal impairment; has not been adequately studied; use with caution.

PROPOFOL:

  • No dosage adjustment necessary.

 

Reference:

Lacerda, Glenda Corrêa Borges de. “Treating Seizures In Renal And Hepatic Failure”. J. epilepsy clin. neurophysiol. 14 (2008): 46-50.

Uptodate.  Accessed 07/12/2016.

 

SIADH

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  • Patients with severe symptoms or SAH at risk for vasospasm will receive hypertonic saline; otherwise the cornerstone of treatment for SIADH is fluid restriction.
  • Acute hyponatremia and/or severe symptoms should have 6 mmol/L corrected over 6 h or until severe symptoms improve.
  • The total correction of Na should not exceed 8 mmol/L over 24 h. Therefore, if 6 mmol/L is corrected in 6 h, the Na should not be increased more than 2 mmol/L in the following 18 h.
  • The total correction of Na is based on the Na deficit which is calculated conservatively with the formula depicted.
  • With improvement of symptoms, the patients can be moved to the less aggressive treatments in the algorithm, until Na reaches 131 mmol/L.

 

Reference

Layon, A. Joseph, Andrea Gabrielli, and William A Friedman. Textbook Of Neurointensive Care. Print.