Hyponatreamia

  • Hyponatraemia is all about ADH typically

  • Isothenuria normal in aging and in AKI/CKD.

    • Urine diulation is active and difficult
    • Normal adult can generate dilute urine - 50mOSM/Kg
    • “Normal” diet is 10mOSM/kg/day, so 70kg male = (10*70)=700/50(daily limit)=14litres
    • Elderly limit ~150 mOSM/kg. Diet intake can be low (tea and toast) e.g. (3*50)/150=1Litre/day. free water over this limit dilutes urine.

  • Hypotonic hyponatraemia requires treatment (probably), so confirm a pOSM if possible.

  • k+ is oncotic too ( and can buffer NA) - 20mmol/KCL = 40ml 3% NaCL - may overcorrect if not aware!

  • Urine Na: >30 mmol/l urinary Na = dry (NB low [Na] diet, diuretics, CKD - poor reabsorbtion (and impaired free water clearance too))

  • Urine Osm: <100 mmmol/L = appropriately dilute. 100 - serum osm = grey area.

    • Remember that a measured osm also measures ineffective osmolues such as Urea or Ethanol - may be artefactually high and mask true hypoosmolar state

  • Non-hypotonic (hyperglycaemia, mannitol, hypertonic radiocontrast,pseudohyponatreamia) - conservative Rx

Correction

  • Hypertonic Saline: 3% 150 mls/20 mins. recheck while giving second bag. target increase of 5mmol/L
  • 0.9% Saline = 154mmol/L, 3% Saline =513mmol/L
  • 1ml/kg/hr 3% NaCL corrects Na ~ 1mmol/l/hr. e.g. 70mls/hr =1. so 150mls = ~2ish.
  • Speed limit: 10/first 24 hrs, 8/24 hrs thereafter
  • Fix overcorrection with a DDAVP clamp as below: 5% glucose and DDAVP 2/4mcg sc as below
  • Once stable - give 3% saline as follows, remembering to substract bolus:

6*(Totalbodywater+1)/(513-initial NA) = total volume - boluses already given. Divide by hours (typically 4). HDU and monitor every 4-6


Osmotic demyelination

Risks: Female, hypokalaemia, chronicity, alcoholism, cirrhosis, malnourishment.

Pseudohyponatreamia

Triglycerides, cholesterol, or protein

Hyperglycaemia correction of Na

This translates into adding 2.4 mmol/l to the measured serum sodium concentration for every 5.5 mmol/l (100 mg/dl) incremental rise in serum glucose concentration above a standard serum glucose concentration of 5.5 mmol/l (100 mg/dl). (Ive seen this as 1.6mmol/L also)

Free water clearance

Useful conceptually (in chronic state), not very quantitativly, and inconvienient outside ITU

Calculation

cH2O = uV - (uOsm x uV)/pOsm


where cH2O = Free Water Clearance

  • where uV = Urine Volume per unit time ( make it a day I guess if 24 hours collection)
  • where uOsm = Urine Osmolality
  • where pOsm = plasma osmolality

Interpretation

Free Water Clearance positive

  • Urine less concentrated than plasma

  • Decreased Antidiuretic Hormone (ADH) Free Water Clearance negative

  • Urine is more concentrated than plasma

  • Increased Antidiuretic Hormone (ADH)

SIADH criteria

SIADH is pretty rare. Be suss.

  • Essential criteria

  • Effective serum osmolality >275 mOsm/kg

  • Urine osmolality >100 mOsm/kg at some level of decreased effective osmolality

  • Clinical euvolaemia

  • Urine sodium concentration >30 mmol/l with normal dietary salt and water intake

  • Absence of adrenal, thyroid, pituitary or renal insufficiency

  • No recent use of diuretic agents

  • Supplemental criteria

    • Serum uric acid >0.24 mmol/l (>4 mg/dl)
    • Serum urea >3.6 mmol/l (>21.6 mg/dl)
    • Failure to correct hyponatraemia after 0.9% saline infusion
    • Fractional sodium excretion >0.5%
    • Fractional urea excretion >55%
    • Fractional uric acid excretion >12%
    • Correction of hyponatraemia through fluid restriction

Desmopressin aka DDAVP

In DI: If intravenous saline solution is administered and desmopressin is withheld at the same time, rapid changes in serum sodium levels may result, which puts the patient at risk for demyelinating lesions.

  • Opinion: In the management of desmopressin-associated hyponatremia with neurologic symptoms, the drug should not be withheld despite the presence of hyponatremia. Instead The medication should be continued while administering intravenous hypertonic saline solution.

DDAVP Clamp: Desmopressin is also used to minimize water excretion during the correction of hyponatremia during water diuresis. When treating hyponatremia, clinicians should monitor closely to avoid free-water diuresis. To prevent ongoing water losses in urine and overly rapid “autocorrection” of serum sodium level, desmopressin can be given to reduce free-water losses.

Overcorrection Panic HDU/ITU-> DDAVP, 2 micrograms IV q8hr & H20

Clamp protocol:

Source: EMcrit

  • DDAVP (2 micrograms IV q8hr) is started immediately and continued until the sodium is close to normal.
  • Sodium is corrected by infusing hypertonic solutions, primarily 3% saline. Of course, hypertonic bicarbonate. For a patient requiring volume resuscitation, a large volume of normal saline could be used as well.
  • The key point is that the sodium is increased by a direct effect of the infused solutions. This differs from approaches based on treatment of the underlying problem and waiting for the kidneys to excrete free water.
  • Oral fluid intake must be restricted while on DDAVP.
  • Potassium supplementation should be taken into account as this is osmotically equivalent to sodium (e.g. 40 mEq KCl tablet is roughly equivalent to ~80ml of 3% NaCl).
  • Medications formulated in D5W should be avoided if possible, or otherwise taken into account (e.g. 100 ml of D5W will negate the effect of ~30ml of 3% NaCl)
  • If volume overload occurs, this may be managed with furosemide.

Contraindications to clamp

  • Psychogenic polydipsia/excessive water intake
  • Hypervolemic hyponatremia (e.g. heart failure, cirrhosis)

DDAVP dose:

SC desmopressin at 2-4 mcg every 8-12 hours or intranasal desmopressin, 20 μg, every 12 hours

  • The hourly urine output should decrease substantially in the first 1 to 2 hours after administration.

  • Urine osmolality should be checked to ensure that urine osmolality has increased; 500- to 600-mOsm/kg range = significant antiaquaretic effect.

Vaptans

Not on European guidelines, no real well established role here. no RCT and hypernatreamia/osmotic demyelination risk. Avoid.

Urea

Only in SIADH, ensure not volume deplete. A bit niche, most evidence from ITU.

  • oral intake of two to three doses of 30 g of urea over 24 hours or infusion of 80 g of urea as a 30% solution over six hours, water restriction (500 mL/24 hr), and sodium supplements (120 to 360 mmole/24 hr).
  • generally safe and well tolerated
  • osmotic diuretic & Salt load, so main risks are overcorrection / volume depletion

58 patients at University of Pittsburgh Medical Center

42 patients in a Belgian ITU


Hypernatreamia

Replace H20

Free water deficit calculator. Thats basically it. No such things as pseudohypernatreamia.

To excrete concentrated water ( i.e. not loose free water and push up your Na) a medullary concentration gradiant,ADH & responsive kidney (lithium/DI etc)

Intake: drinking the ocean, hypertonic saline, primary hyperaldo

If not thirsty - hypothalamic lesion?

DI & Polyuria

In patients with polyuria, diabetes insipidus is very unlikely if urine osmolality is >700 mOsmol/kg

nephrogenic - lithium, hypercalcamia hypoK, medullary cystic disease, sickle cell, ceongentical, post obstructive

Central - trauma, surgery, invasive, booze

Give 2-4 mcg ddavp SC and monitor uOSM & vol every 30 mins for 2 hours. if Uosm increases = concentrating urine = responding = central. can be blunted due to chronic washout if longstanding ( and thus harder to coentrated due to loss of gradiant). should increment by 50% to outrule nephrogenic.

  • Urine osm > 600 - concentrating ok, ?GI/other loss ? intake
  • Urine osm 300-600 - partal DI. ol, CKD, post obstructive
  • Urine osm = pOSM (~300) - osmotic diuresis? NB Urea is actually an effective osm in urine ( cant make it past tubular epithelium) in contrast to in the body!
  • Urine osm <pOSM - DI

Cerebral Salt wasting

May have high urinary Cl-


Nephrogenic DI

Paradoxical role for HCTZ

  • blockade of the Na-Cl cotransporter in the distal tubule leads to a decrease in GFR via Na/water secretion- > increased Na and water reabsorbotion in PT -> less delivery to CD where the concentratign issue is due to AQP issues
  • May increase AQP channels and ENAC
  • In Lithium induced DI , same paper showed reversal of downregulated AQP2 and increased DI

NSAIDs may help by reducing reducing the diuretic effect of renal prostaglandins

Key Papers


Nature Reviews Nephrology: DI.


Desalination
  • 22 women post uncomplicated gyne surgery - given saline / Hartmans. s[Na] dropped in 21/22.
  • Hyponatremia was generally caused by generation of electrolyte-free water during excretion of hypertonic urine-a desalination process. ADH at it again.


Sodium Restriction

Evidence for restriction, especially in people with a reasonable intake is pretty weak - K+ is likely more important

Sodium-HF

low salt dietary intervention in self reportedly low intake population with limited baseline info

TLDR: poorly executed study, stopped due to futility. Probably no role for intensive dietary intervention in pateints with reasonable sodium intake.