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:

c

 

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.

 

 

Venous Blood Gas – VBG-ABG correlation

Venous blood gas can be used toestimate systemic CO2 and pH levels.

Possible sites of VBG:

  1. peripheral venous sample (from venipuncture)
  2. central venous sample (from central venous catheter)
  3. mixed venous sample (from distal port of PAC)

Values from VBG:

  1. PvO2 – venous oxygen tension
  2. PvCO2 – venous carbon dioxide tension
  3. pH
  4. SvO2 – oxyhemoglobin saturation
  5. HCO3 – serum bicarbonate

PvCO2, pH, HCO3 – assess ventilation and/or acid-base status

SvO@ – guides resuscitation

PvO2 – no value

 

Correlations:

  1. Central venous sample
    1. pH – 0.03 to 0.05 pH units lower than arterial pH
    2. PvCO2 – 4-5 mm Hg higher than PaCO2
    3. HCO3 – little or no increase
  2. Mixed venous sample – similar tocentral venous sample
  3. peripheral venous sample
    1. pH – 0.02 to 0.04 pH units lower than arterial pH
    2. HCO3 –  1-2 mEq/L higher
    3. PvCO2 – 3-8 mm Hg higher than PaCO2

*varies with hemodynamic stability

 

Reference:

Uptodate.com. (2018). UpToDate. [online] Available at: https://www.uptodate.com/contents/venous-blood-gases-and-other-alternatives-to-arterial-blood-gases?search=venous%20blood%20gas&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 [Accessed 22 Oct. 2018].

Equations for Phenytoin Dosing and Monitoring

#1.  loading dose for subtherapeutic phenytoin concentration:

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#2. adjust for renal disease

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#3. adjust for hypoalbuminemia

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#4. adjust in elderly and critically ill with hypoalbuminemia

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**Vd = volume of distribution (0.5-1 L/kg)

 

Reference:

Tesoro, E. P. and G. M. Brophy. “Pharmacological Management Of Seizures And Status Epilepticus In Critically Ill Patients”. Journal of Pharmacy Practice 23.5 (2010): 441-454.

**Thanks to Benjamin Wee (Clinical Pharmacist @ Lenox Hill Hospital) for giving me this resource.

Bicaudate Index

Diagram showing the method for measuring the bicaudate index (A / B). A = the width of the frontal horns at the level of the caudate nuclei; B = the diameter of the brain at the same level.

 

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The bicaudate index is a commonly used linear measure of the lateral ventricles. To account for the natural changes in the size of ventricles with aging, BCI is then divided by the upper limits of ‘normal’ for age to calculate the relative bicaudate index.

Diagnosis of hydrocephalus is established when RBCI is >1. Normative values determined from subjects without neurological disease, in the mid to late 1970s.

 

Divide the width of the frontal horns, at the level of the caudate nuclei, by the corresponding diameter of the brain. Perform measurement on the cut which included the Foramen of Monro.  If the foramen of Monroe is in between two cute, use mean value for of the two cuts.

 

Bicaudate index plotted against age. The density ellipsoid includes 95% of the data points.

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Normal BCI values, stratified by age group, in a cohort of SAH patients without co-existing hydrocephalus.

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References:

Gijn, Jan van et al. “Acute Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage”. Journal of Neurosurgery 63.3 (1985): 355-362.

Dupont, Stefan and Alejandro A Rabinstein. “CT Evaluation Of Lateral Ventricular Dilatation After Subarachnoid Hemorrhage: Baseline Bicaudate Index Balues”. Neurological Research 35.2 (2013): 103-106.

 

CSF WBC Correction for Traumatic Tap

If peripheral WBC is normal, then use ratio of 1:500 or 1:750.

If peripheral WBC abnormal, then use the following formula:

  • WBCcsf = WBCblood x RBCcsf / RBCblood
  • or  WBCc * RBCb = WBCb*RBCc
  • or WBCc/RBCc = WBCb/RBCb

The result is the number of artificially introduced WBCs.

True WBCcsf is then calculated by subtracting the artificially introduced WBCs from the actual WBCcsf

Reference:

“WBC Correction For Traumatic Tap – Labce.Com, Laboratory Continuing Education”. Labce.com. N.p., 2016. Web. 17 Aug. 2016.

HBA1C

Notes:

  1. RBCs have a life cycle of 8-12 weeks.
  2. HbA1C is formed by glycation (attachment of glucose) to Hb and reflects glucose concentration of the previous 2-3 months.
  3. HbA1C diagnostic of DM – 6.5% (48mmol/mol)
  4. goal of DM management – <7%

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Factors that alter the HbA1C value:

  1. erythrocyte life span
    • increased lifespan – increases time RBC is exposed to glucose, increases HbA1C falsely, (ex. splenectomy)
    • decreased lifespan – HbA1C decreased (ex. hemolytic anemia)
  2. erythropoiesis
    • decreased erythropoiesis – increases mean age of RBC, increases HbA1C level (ex. iron deficiency anemia)
    • severe CKD decreases erythropoietin levels
  3. severe hypertriglyceridemia and chronic alcoholism
    • interferes with assay
  4. Hb variants – yields inaccurate results
  5. genetic factors or the “glycation gap”
    1. genes that affect RBC life span or glycation

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ALTERNATIVE TESTING METHODS

 

  1. glycated albumin and fructosamine (measures all glycated serum protein)
    1. half life of albumin is 14-21 days; all glycated serum protein tests reflect average blood glucose concentrations over the previous 2-3 weeks
    2. not affected by RBC disorders but by serum protein abnormalities (i.e. nephrotic syndrome)
  2. daily fingerstick
  3. continuous glucose monitor
  4. serum 1,5 anhydroglucitol (1,5-AG) test

 

CONVERSION A1C EST AVE BLOOD GLUCOSE:

The formula for converting A1C to an estimated average blood glucose level, according to the American Diabetes Association, is (28.7 x A1C) – 46.7 = estimated average glucose.

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Conversion table (A1C to EAG)

 

References

O’Keeffe, Derek T., Spyridoula Maraka, and Robert A. Rizza. “Hba 1C In The Evaluation Of Diabetes Mellitus”. JAMA 315.6 (2016): 605. Web. 13 Feb. 2016.

Nhrmc.org,. N.p., 2016. Web. 13 Feb. 2016.  https://www.nhrmc.org/~/media/files/ diabetes-health-plan/class-materials/diabetes-overview-class/conversion-table-revised-12-30-14.pdf?la=en

 

How much hypertonic solution?

To determine how much hypertonic solution to give a patient with hyponatremia:

  1.  calculate sodium deficit (mEq) = weight (kg) x 0.6 x (desired Na – actual Na)
    1. use 0.5 for females
    2. desired sodium in mEq/L
  2. calculate the safe rate of sodium correction for the patient in mEq/hr (0.5-1 mEq/L/hr) = weight (Kg) x 0.6 x 1.0 (rate of correction desired)
  3. 3% hypertonic saline contains 513 mEq/L; 2% contains 342 mEq/L; 1.5% contains 256 mEq/L and 0.9% contains 154 mEq/L
  4. desired rate = (safe rate of correction / 513) x 1000
  5. infusion time (hrs) = sodium deficit (mEq) / safe rate of correction (mEq/hr)

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Marino: estimate initial infusion rate of 3% NaCl by multiplying patient’s KgBW by the desired rate of increase in plasma Na. Example: 70Kg male, desired rise in plasma is 0.5 mEq/L per hour, then infusion rate = 70×0.5 = 35 ml/Hr

References

Globalrph.com,. “Sodium Chloride 3% –  Intravenous (IV) Dilution”. N.p., 2016. Web. 30 Jan. 2016.

Marino, 2014. The ICU Book.

DO2 Equation

The human body does not care much about pO2 or FiO2.  What is important to the body is the amount of oxygen actually being delivered to the tissues.  Focusing on the pO2 in the ABG results, or the FiO2 settings of O2 support, without understanding how oxygen is delivered to body tissues can have dire consequences.

The formula below summarizes the various factors that contribute to tissue oxygen delivery, and is worthwhile to remember when thinking about a patient’s oxygen status.

DO2 = CO x (sO2 x ceHb x 1.39) + (PaO2 x 0.03)

  • DO2 = total blood oxygen content
  • sO2 = oxygen saturation
  • ceHb = effective Hb concentration

 

 

Oxygen-carrying Capacity of Hb [BO2]

Potential oxygen carrying capacity – determined by total Hb concentration [ctHb, measured in ABG – measures all species of Hb, including carboxyHb].  

Actual oxygen carrying capacity [BO2] – maximum amt of Hb-bound oxygen per unit volume of blood [mmol/L], the amt of oxygent present in a volume of blood if all the effective Hb molecules (ceHb) were 100% saturated; or in formula = ceHb x 100%sO2

Therefore BO2 ~ ctHb – cdysHb (non O2-carrying Hb].

BO2 was found to be 1.39 ml/g.  [Different textbooks give values between 1.3 to 1.39 g/mL]

 

The equation usually used to describe the rate of oxygen delivery is as follows:

DO2 equation

This equation will not be applicable when levels of dys-hemoglobins (e.g. metHb, carboxyHb, etc) are high.  A better formula to describe DO2, taking into account only the concentration of effective Hb would be:

a better DO2 equation

 

Example:

  • ceHb = 150g/L
  • Wt = 70 Kg
  • PaO2 = 100
  • SO2 = 100%
  • CO = 5 L/min

DO2 = 5 × (1.39 × 150 × 1 + (0.003 × 100))  = 1044 ml/min [15ml, dissolved, 1029ml bound].

Total rate of O2 delivery is usually around 15ml/kg/min.

 

Implications of this formula:

  1. Oxygen solubility is poor at body temperature, ~0.03ml/L/mmHg.  In simple terms, In 1 L of blood (at an alveolar O2 of 100mmHg), there is only 3ml/L of dissolved oxygen.  Or, 1% of total oxygen content is dissolved in blood while the remaining 99% is bound to Hb.  Therefore, improving paO2 by itself, has very little effect on tissue oxygenation. [Caveat: Concept does not apply to hypothermia or hyperbaric oxygen therapy]
  2. At 100% saturation, there is ~1.39 ml of O2 per gram of Hb.
  3. At a Hb of 150 g/L, there is ~200ml of O2 in every Liter of blood.
  4. In the presence of inadequate tissue oxygenation – do not think only about increasing PaO2 or FiO2.  There are other (more important) factors that can be manipulated, s.a. heart rate, stroke volume, hematocrit and oxygen saturation.

References

Deranged Physiology,. “The Oxygen – Carrying Capacity Of Whole Blood”. N.p., 2015. Web. 21 Jan. 2016.