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1. Hyponatremia and Hypernatremia Conor Gough HO – III 2008-2009

2. Hyponatremia • Defined as sodium concentration < 135 mEq/L • Generally considered a disorder of water as opposed to disorder of salt • Results from increased water retention • Normal physiologic measures allow a person to excrete up to 10 liters of water per day which protects against hyponatremia • Thus, in most cases, some impairment of renal excretion of water is present

3. Causes • Normal ADH response to low sodium is to be suppressed to allow maximally dilute urine to be excreted thereby raising serum sodium level • Psuedohyponatremia – High blood sugar (DKA) or protein level (multiple myeloma) can cause falsely depressed sodium levels • Causes of Hyponatremia can be classified based on either volume status or ADH level • Hypovolemic, Euvolemic or Hypervolemic • ADH inappropriately elevated or appropriately suppressed

4. ADH suppresion • Conditions which ADH is suppressed • Primary Polydipsia • Low dietary solute intake “Tea and Toast syndrome” or “Beer Potomania” • Advanced Renal Failure

5. ADH elevation • Conditions which ADH is elevated • Volume Depletion • True volume depletion (i.e. bleeding) • Effective circulating volume depletion (i.e. heart failure and cirrhosis) • Exercised induced hyponatremia • Thiazide Diuretics • Adrenal insufficiency • SIADH

6. First step in Assessment: Are symptoms present? • Hyponatremia can be asymptomatic and found by routine lab testing • It may present with mild symptoms such as nausea and malaise (earliest) or headache and lethargy • Or it may present with more severe symptoms such as seizures, coma or respiratory arrest

7. Presentation determines if immediate action is needed • If severe symptoms are present, hypertonic saline needs to be administered to prevent further decline • If severe symptoms are not present, can start by initiating fluid restriction and determining cause of hyponatremia • Oral fluid restriction is good first step as it will prevent further drop in sodium • NOTE: This does not mean that you can’t give isotonic fluids to someone who is truly volume depleted

8. WHAT NEXT? • With no severe symptoms and fluid restriction started, next step is to assess volume status to help determine cause • Hypovolemic – urine output, dry mucous membranes, sunken eyes • Euvolemic – normal appearing • Hypervolemic – Edema, past medical history, Jaundice (cirrhosis), S3 (CHF)

9. Volume status helps predict cause • Hypovolemia • True Volume Depletion • Adrenal insufficiency • Thiazide overdose • Exercised induced hyponatremia • Euvolemia • SIADH • Primary Polydipsia • Hypervolemia • Cirrhosis and CHF

10. Workup for Hyponatremia • 3 mandatory lab tests • Serum Osmolality • Urine Osmolality • Urine Sodium Concentration • Additional labs depending on clinical suspicion • TSH, cortisol (Hypothryoidism or Adrenal insufficiency) • Albumin, BMP, triglycerides and SPEP (psuedohyponatremia, cirrhosis, MM)

11. How to interpret the tests? • Serum Osmolality • Can differentiate between true hyponatremia, pseudohyponatremia and hypertonic hyponatremia • Urine Osmolality • Can differentiate between primary polydipsia and impaired free water excretion • Urine Sodium concentration • Can differentiate between hypovolemiahyponatremia and SIADH

12. Additional Tests • TSH – high in hypothyroidism • Cortisol – low in adrenal insufficiency, though may be inappropriately normal in infection/stressful state, therefore should get Corti-Stim test to confirm • Head CT and Chest Xray – May see evidence of cerebral salt wasting or small cell carcinoma which can both cause hyponatremia

13. And of course…the not so common • Iatrogenic infusion of hypotonic fluids (“Surgeon sign”) • Ecstasy use – increased water intake with inappropriate ADH secretion • Underlying infections • NSIAD – Nephrogenic syndrome of inappropriate antidiuresis – Hereditary disorder that presents with low sodium levels in newborn males with undetectable ADH levels • Reset Osmostat – Occurs in elderly and pregnancy where regulated sodium set point is lowered

14. SIADH: Important concept to understand • Caused by various etiologies • CNS disease – tumor, infection, CVA, SAH, DTs • Pulmonary disease – TB, pneumonia, positive pressure ventilation • Cancer – Lung, pancreas, thymoma, ovary, lymphoma • Drugs – NSAIDs, SSRIs, diuretics, TCAs • Surgery - Postoperative • Idopathic – most common

15. Main diagnostic criteria for SIADH • Clinical Euvolemia • Hypotonic Hyponatremia • Normal hepatic, renal and cardiac function • Normal thyroid and adrenal function • Urine osmolality greater than 100 mOsm/kg though generally greater than 400-500 mOsm/kg in setting of low serum osmolality (AKA inappropriate) • Urine sodium level greater than 20 mEq/L

16. Treatment is based on symptoms • Patients with serum sodium above 120 are generally asymptomatic • Symptoms tend to occur at serum sodium levels lower than 120 or when a rapid decline in sodium levels occur • Patients can have mild symptoms at sodium concentrations of 110-115 mEq/L when this level is reached gradually

17. Severe symptoms present • As stated earlier, symptoms dictate treatment • If severe symptoms are present, starting bolus of 100 ml of 3% hypertonic saline which generally raise serum sodium level by 2-3 mEq/L • Goals for correction: • 1.5 to 2 mEq/L per hour for first 3-4 hours until symptoms resolve • Increase by no more than 10 mEq/L in first 24 hrs • Increase by no more than 18 mEq/L in first 48 hrs

18. What if little to no symptoms are present? • Oral fluid restriction is the first step • No more than 1500 mL per day • NOTE: This only pertains to oral fluid, isotonic IV fluids do not count towards fluid intake • If volume depletion is present, isotonic (0.9%) saline can be given intravenously • Careful monitoring should be used whether symptoms are present or not • Serum sodium levels should be drawn every 4-6 hours or more frequently if hypertonic saline is used

19. Formulas that may help: How much sodium does the patient need? • Sodium deficit = Total body water x (desired Na – actual Na) • Total body water is estimated as lean body weight x 0.5 for women or 0.6 for men

20. How about an example: • 60 kg woman with sodium level of 116 • How much sodium will bring him up to 124 in the next 24 hours? • Sodium needed = 0.5 x 60 x (124-116) = 240 • Hypertonic saline contains 500 mEq/L of sodium • Normal saline contains 154 mEq/L of sodium

21. Example (continued) • The patient needs 240 mEq in next 24 hours • That averages to 10 mEq per hour or 20 mL of hypertonic saline per hour • However, this will only raise the serum sodium by 0.33 per hour therefore, increasing the rate 60 mL to 90 mL will produce the desired rate of serum sodium increase of 1.0 to 1.5 mEq per hour until symptoms resolve

22. What if the sodium increases too fast? • The dreaded complication of increasing sodium too fast is Central Pontine Myelinolysis which is a form of osmotic demyelination • Symptoms generally occur 2-6 days after elevation of sodium and usually either irreversible or only partially reversible • Symptoms include: dysarthria, dysphagia, paraparesis, quadriparesis, lethargy, coma or even seizures

23. Risk Factors for demyelination • Rate of correction over 24 hours more important than rate of correction in any one particular hour • More common if sodium increases by more than 20 mEq/L in 24 hours • Very uncommon if sodium increases by 12 mEq/L or less in 24 hours • CT but preferably MRI to diagnose demyelination if suspected, though imaging studies may not be positive for up to 4 weeks after initial correction

24. Treatment Options • CPM is associated with poor prognosis • Prevention is key • Small studies have shown that plasmapharesis done immediately after diagnosis may improve clinical outcomes

25. Summary of Hyponatremia • Hyponatremia has variety of causes • Treatment is based on symptoms • Severe symptoms = Hypertonic Saline • Mild or no symptoms = Fluid restriction • Overcorrection, more than 12 mEq increase in 24 hours must be avoided with monitoring • Serum Osmolality, Urine Osmolality and Urine sodium concentration are initial tests to order

26. Moving on to Hypernatremia • Produced by either administration of hypertonic fluids or much more frequently, loss of thirst • Because of extremely efficient regulatory mechanisms such as ADH and thirst, hypernatremia generally occurs only in people with prolonged lack of thirst mechanism • Patients with loss of ADH (Diabetes Insipidus) usually can compensate with increased fluid intake

27. Causes of Hypernatremia • Insensible and sweat losses • GI losses • Diabetes Insipidus (both central and nephrogenic) • Osmotic Diuresis – DKA or HHNK • Hypothalamic lesions which affect thirst function – Causes include tumors, granulomatous diseases or vascular disease • Sodium Overload – Infusion of Hypertonic sodium bicarbonate for metabolic acidosis

28. Symptoms of Hypernatremia • Initial symptoms include lethargy, weakness and irritability • Can progress to twitching, seizures, obtundation or coma • Resulting decrease in brain volume can lead to rupture of cerebral veins leading to hemorrhage • Severe symptoms usually occur with rapid increase to sodium concentration of 158 mEq or more • Sodium concentration greater than 180 mEq are associated with high mortality

29. Diagnosis of Hypernatremia • Same labs as workup for hyponatremia: Serum osmolality, urine osmolality and urine sodium • Urine sodium should be lower than 25 mEq/L if and water and volume loss are cause. It can be greater than 100 mEq/L when hypertonic solutions are infused or ingested • If urine osmolality is lower than serum osmolality then DI is present • Administration of DDAVP will differentiate • Urine osmolality will increase in central DI, no response in nephrogenic DI

30. Treatment of Hypernatremia • First, calculate water deficit • Water deficit = CBW x ((plasma Na/desired Na level)-1) • CBW = current body water assumed to be 50% of body weight in men and 40% in women • So let’s do a sample calculation: • 60 kg woman with 168 mEq/L • How much water will it take to reduce her sodium to 140 mEq/L

31. Calculation continued • Water deficit = 0.4 x 60 ([168/140]-1) = 4.8 L • But how fast should I correct it? • Same as hyponatremia, sodium should not be lowered by more than 12 mEq/L in 24 hours • Overcorrection can lead to cerebral edema which can lead to encephalopathy, seizures or death • So what does that mean for our patient? • The 4.8 L which will lower the sodium level by 28 should be given over 56-60 hours, or at a rate of 75-80 mL/hr • Typical fluids given in form of D5 water

32. Summary of Hypernatremia • Loss of thirst usually has to occur to produce hypernatremia • Rate of correction same as hyponatremia • D5 water infusion is typically used to lower sodium level • Same diagnostic labs used: Serum osmolality, Urine osmolality and Urine sodium • Beware of overcorrection as cerebral edema may develop

33. Questions?