American College of Physicians

1. American College of Physicians Panama City February 3, 2012 Hyponatremia – Therapeutic Challenges Robert G. Luke, M.D., M.A.C.D.

2. DEPLETION AND EXCESS Salt – ECF Volume H20 – Osmolality = ECF SALT/ water  ECF Vol./ shock CNS Presentation  Edema P[Na] Useless P[Na] useful

3. Question 7 An increasingly breathless and confused man of 50 years is admitted with a large pleural effusion, normal cortisol and TSH serum levels, and no edema. Vital signs are normal and he is not hypoxic. Lab data:

4. What is the most likely mechanism/cause of hyponatremia? • ECF volume contraction • L.V. Failure • SIADH • ECF Vol. Expansion • None of the above

5. Types of Hyponatremia • Pseudohyponatremia (Rarely < 130) • Hypertonic (Plasma Glucose ) • Hypotonic

6. HYPOTONIC HYPONATREMIA • ECF Vol. • Edematous States • Euvolemic(SIADH) • Thiazides

7. UOSM IS BIOASSAY FOR ADH! If PNa, Uosm should be <100 If not, non osmolar ADH release e.g. ECF volume 

8. BRAIN RESPONSE TO OSMOLALITY  Acute HYPONATREMIA– 24 Hr(Yyou can correct quickly) BUT Correct slowly if chronic hyponatremia (duration unknown or 2-3 days +) to avoid the OSMOTIC DEMYELINIZATION SYNDROME; correction rate should not Exceed 12 meq per 24 hours.

9. Question 7 An increasingly breathless and confused man of 50 years is admitted with a large pleural effusion, normal cortisol and TSH serum levels, and no edema. Vital signs are normal and he is not hypoxic. Lab data:

10. CLINICAL QUESTIONS TO ASK • What type of hypotonic hyponatremia? (4) types • Is patient symptomatic? (2a) due to hyponatremia? • Is hyponatremia acute or chronic? • What is kidney doing? • Treatment: • Remove underlying cause (e.g. a drug) OR • Water restriction or inhibit ADH(VAPTANS) OR • Isotonic Saline OR • Hypertonic saline ± furosemide OR • Watch KIDNEY correct AND • Intervene if correcting too quickly-hypotonic fluids or aqueous ADH

11. How to correct Hyponatremia • This patient has chronic hyponatremia with some CNS symptoms. Assuming Cardiac failure and ECF volume depletion are ruled out, give Hypertonic saline to bring up Patient’s plasma [Na] by 5-10 % quickly. If CNS symptoms do not improve, seek other causes fo confusion and slow [Na] correction rate to < 0.6 mEq/hour.

12. When to use furosemide with hypertonic saline? • In euvolemic hypotonic hyponatremia with CNS symptoms, and a Uosm> 500, a loop diuretic impairs renal concentrating ability and reduces Uosm even if ADH secretion continues. This increases the difference between the infused [Na] and urinary [Na] and increases correction rate. Beware of isotonic saline when Uosm is high-it might make the plasma [Na] LOWER!

13. Inhibit anti-diuretic hormone (ADH); expensive CONIVAPTAN- INTRAVENOUS AND INHIBITS V1 AND V2 RECEPTORS TOLVAPTAN-ORAL AND INHIBITS V2(RENAL) RECEPTOR ONLY Which would you use here? Vaptans = Aquaretic agents

14. CLINICAL QUESTIONS TO ASK • What type of hypotonic hyponatremia? (4) types • Is patient symptomatic? (2a) due to hyponatremia? • Is hyponatremia acute or chronic? • What is kidney doing? • Treatment: • Remove underlying cause (e.g. a drug) OR • Water restriction or inhibit ADH(VAPTANS) OR • Isotonic Saline OR • Hypertonic saline ± furosemide OR • Watch KIDNEY correct AND • Intervene if correcting too quickly-hypotonic fluids or aqueous ADH

15. CLINICAL QUESTIONS TO ASK • What type of hypotonic hyponatremia? (4) types • Is patient symptomatic? (2a) due to hyponatremia? • Is hyponatremia acute or chronic? • What is kidney doing? • Treatment: • Remove underlying cause (e.g. a drug) OR • Water restriction or inhibit ADH(VAPTANS) OR • Isotonic Saline OR • Hypertonic saline ± furosemide OR • Watch KIDNEY correct AND • Intervene if correcting too quickly-hypotonic fluids or aqueous ADH

16. Post appendectomy a woman aged 29 years is found obtunded at 24 hours post operatively. She is receiving hypotonic fluids intravenously and had a normal renal electrolyte profile prior to surgery. Clinically she is euvolemic and disoriented. Lab studies:

17. CLINICAL QUESTIONS TO ASK • What type of hypotonic hyponatremia? (4) types • Is patient symptomatic? (2a) due to hyponatremia? • Is hyponatremia acute or chronic? • What is kidney doing? • Treatment: • Remove underlying cause (e.g. a drug) OR • Water restriction or inhibit ADH(VAPTANS) OR • Isotonic Saline OR • Hypertonic saline ± furosemide OR • Watch KIDNEY correct AND • Intervene if correcting too quickly-hypotonic fluids or aqueous ADH

18. TO CALCULATE DOSE OF HYPERTONIC SALINE(approximately) Infused [Na+] – Patient [Na+] ÷ Total Body Water (50% Body Wt) Example: (3% saline)500 – 100 (meq) = 400 = 10 meq if 1 Liter given 40 (L) 40 100 ml 3% saline in this patient increases [Na+] by1 meq/L ***** A rise of 5-8 meq/L is enough to correct CNS symptoms ***** . . .

19. A 68 year old female is admitted with drowsiness and an episode of syncope. She has been taking Hydrochlorothiazide 25mg and following a low salt diet. On admission she weighs 60kg and has postural hypotension and sinus tachycardia. Her renal profile is:

20. Mechanisms of Drug-Induced Hyponatremia • Stimulate ADH release Example: Vincristine • Potentiate effects of ADH on kidney Example: NSAIDS • ADH – like effect Example: Oxytocin 4. Impair free water excretion Example: Thiazides PLUS—always– high intake of WATER or hypotonic fluids

21. WHAT CAN KIDNEY DO BY ITSELF ? . . . Renal free water excretion after cessation of ADH secretion = at least 500 ml/hour with Uosm < 100 mosm/L (assume sodium free urine and patient weighs 80Kg and Plasma sodium 100) Thus total body water will decrease in 2 hours by (1/40 x 100)% = 2.5% and Plasma sodium will increase by 2.5meq/L . . .

22. Risk Factors for Osmotic Demyelinization Syndrome(Formerly Called “Pontine Myelinolysis”)after too rapid correction of plasma sodium concentration • Hypoxia • Malnutrition • K Depletion • Elderly and children • Pre-Menopausal • Alcoholism

23. Common Causes of Hyponatremia in Elderly

24. Effects of Chronic Hyponatremia in Elderly

25. A patient has been seen for medical consultation after subarachnoid hemorrhage because of confusion and continuing CNS abnormalities. The BP is 110/70 and the pulse rate 100 per minute. There is no edema and chest X-ray and EKG are within normal limits. Lab data:

26. CLINICAL QUESTIONS TO ASK • What type of hypotonic hyponatremia? (4) types • Is patient symptomatic? (2a) due to hyponatremia? • Is hyponatremia acute or chronic? • What is kidney doing? • Treatment: • Remove underlying cause (e.g. a drug) OR • Water restriction or inhibit ADH(VAPTANS) OR • Isotonic Saline OR • Hypertonic saline ± furosemide OR • Watch KIDNEY correct AND • Intervene if correcting too quickly-hypotonic fluids or aqueous ADH

27. Diagnosis? • Cerebral Salt Wasting • SIADH • A.R.F. & Dilutional Hyponatremia • None of the above

28. Question 6 A 45 year old male is “found down” at home. Renal profile: He has left bundle branch block and left ventricular hypertrophy and BP is 160/100. He has 1+ edema.

29. Following the completion of a marathon, a 32 year old female was admitted with pulmonary edema which is shown to be noncardiogenic. She is hypoxic and is intubated. An MI is ruled out. She has been taking NSAIDS. Initial lab:

30. Thank you for your attention QUESTIONS ?