Hyponatremia and hypernatremia Runolfur Palsson, MD, FACP, FASN EFIM President-Elect Icelandic Society of Internal Medicine

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1 Hyponatremia and hypernatremia Runolfur Palsson, MD, FACP, FASN EFIM President-Elect Icelandic Society of Internal Medicine 17 June, 2016 ESIM 2016, Sardinia

2 Disclosures Nothing to disclose LANDSPITALI THE NATIONAL UNIVERSITY HOSPITAL OF ICELAND DIVISION OF NEPHROLOGY

3 Hyponatremia and hypernatremia are disorders of water balance!

4 Osmolality of the body fluids The serum osmolality is kept constant at ~285 mosm/kg by matching water excretion and intake Osmolality is equal in all body fluid compartments Serum osmolality can be calculated: Osmolality = 2 x SNa + + glucose + urea Effective osmolality = 2 x SNa +

5 Excretion of free water by the kidney Sumit Kumar & Tomas Berl

6 Action of arginine vasopressin on the renal principal cell Sumit Kumar & Tomas Berl

7 Regulation of vasopressin secretion Sumit Kumar & Tomas Berl

8 The relationship between plasma vasopressin and urine osmolality Ball, Ann Clin Biochem 2007;44:417 31

9 The role of dietary solute intake Healthy individuals on a normal diet excrete mosmoles of solute in the urine daily If minimum urine osmolality is 60 mosm/kg, then maximum urine output will be L Poor dietary intake can lower the daily urinary solute excretion to below 250 mosmoles, resulting in significant reduction in urine volume Examples: Beer drinker s potomania - high water intake, low dietary protein Tea and toast hyponatremia - a diet that is deficient in salt and protein LANDSPITALI THE NATIONAL UNIVERSITY HOSPITAL OF ICELAND DIVISION OF NEPHROLOGY

10 Effects of hyponatremia on the brain and adaptive responses Androgue & Madias, N Engl J Med 2000;342:1581 9

11 Acute hyponatremia and brain edema Hyponatremic brain edema Normal brain Ayus et al, Ann Int Med 2000;132:711 4

12 Osmotic demyelination syndrome Normal brain Central pontine myelinolysis Demyelination lesion Sveinsson & Palsson, Icelandic Med J 2008;94:665 71

13 Treating hyponatremia: damned if we do and damned if we don t Thomas Berl Hyponatremia places the treating physician between a rock and a hard place Richard Sterns

14 European Society of Endocrinology, European Society of Intensive Care Medicine, European Renal Association European Dialysis and Transplant Association (2014)

15 Classification of hyponatremia according to severity (Spasovski et al., Nephrol Dial Transplant 2014;0:1 39) Mild hyponatremia: SNa mmol/l Moderate hyponatremia: SNa mmol/l Profound hyponatremia: SNa + <125 mmol/l LANDSPITALI THE NATIONAL UNIVERSITY HOSPITAL OF ICELAND DIVISION OF NEPHROLOGY

16 Causes of hypotonic hyponatremia Impaired renal water excretion Decreased extracellular fluid volume Increased extracellular fluid volume - Heart failure - Cirrhosis - Advanced renal failure Normal extracellular fluid volume - Thiazide diuretics - Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) - Adrenal insufficiency - Hypothyroidism - Low dietary solute intake Excessive water intake Psychogenic polydipsia Associated with prolonged exercise CNS disorders (including acute psychosis) Cancer Medications Pulmonary disease Miscellaneous Postoperative state Pain Severe nausea

17 Clinical features of hyponatremia Acute hyponatremia (<48 hrs) Seizures Coma Respiratory distress Chronic hyponatremia (>48 hrs) Frequently mild or no symptoms Headache Restlessness Muscle cramps Nausea and vomiting Lethargy Confusion and disorientation Severe cerebral edema Risk of death from untreated hyponatremia Adaptation minimizes brain swelling Risk of injury from overtreated hyponatremia

18 Diagnosis of hyponatremia (Spasovski et al., Nephrol Dial Transplant 2014;0:1 39) Diagnostic criteria for SIADH: Effective serum osmolality <275 mosm/kg Urine osmolality >100 mosm/kg Clinical euvolemia Urine Na + >30 mmol/l with normal dietary salt and water intake Absence of adrenal, thyroid, pituitary or renal insufficiency No recent use of diuretic agents

19 Treatment of hyponatremia with severe symptoms (Spasovski et al., Nephrol Dial Transplant 2014;0:1 39)

20 How much hypertonic saline should be administered? Androgue-Madias formula: Change in serum Na + = InfNa + SNa + Total body water + 1 Estimates the effect of 1 liter of any fluid infused on SNa + Assumes all of the infusate is retained; does not consider urine losses of electrolytes or water Androgue & Madias, N Engl J Med 2000;342:1581 9

21 Chronic hyponatremia: rate of correction and outcome Clinical observations suggest that the risk of demyelination injury of the brain is increased if the rate of correction of the SNa + is faster than 12 mmol/l in the first 24 hours and 18 mmol/l in 48 hours This is particularly important in patients with extreme hyponatremia (SNa + <105 mmol/l) LANDSPITALI THE NATIONAL UNIVERSITY HOSPITAL OF ICELAND DIVISION OF NEPHROLOGY

22 Chronic hyponatremia without severe symptoms Spasovski et al., Nephrol Dial Transplant 2014;0:1 39

23 Treatment of sustained euvolemic and hypervolemic hyponatremia Conventional treatment options are suboptimal because of limited efficacy and poor safety and tolerability Identify and treat the underlying cause Fluid restriction L/day is the mainstay but poorly tolerated long-term Drug therapies: Loop diuretic plus increased salt intake Demeclocycline mg/day Lithium mg/day Urea 30 g/day Vasopressor receptor antagonist LANDSPITALI THE NATIONAL UNIVERSITY HOSPITAL OF ICELAND DIVISION OF NEPHROLOGY

24 What level of fluid restriction should be recommended? UNa + + UK + Fluid restriction SNa + >1 <500 ml per day ml per day <1 <1000 ml per day

25 Treatment of hypovolemic hyponatremia Restore extracellular fluid volume using intravenous infusion of 0.9% NaCl or balanced crystalloid solution at ml/kg/hr Eliminates volume stimulus for vasopressin secretion Unpredictable onset of water diuresis Avoid overcorrection of SNa + In SIADH, isotonic saline is ineffective and may lower the SNa + LANDSPITALI THE NATIONAL UNIVERSITY HOSPITAL OF ICELAND DIVISION OF NEPHROLOGY

26 Reversal of inadvertent overcorrection of hyponatremia Perianayagam et al, Clin J Am Soc Nephrol 2008;3:331 6

27 Hypernatremia SNa + >145 mmol/l Persistent hypernatremia is caused by: Defect in thirst mechanism Limited access to free water (e.g. infants or adults with impaired mental status) Clinical features of acute severe hypernatremia (SNa + >160 mmol/l) range from irritiability and restlessness to seizures and coma Signs of volume depletion are frequently present LANDSPITALI THE NATIONAL UNIVERSITY HOSPITAL OF ICELAND DIVISION OF NEPHROLOGY

28 Causes of hypernatremia Hypovolemic hypernatremia (loss of hypotonic fluid) Euvolemic hypernatremia (pure water loss) Cutaneous loss: Sweating, burns Gastrointestinal loss: Vomiting, nasogastric drainage, enterocutaneous fistula, diarrhea, use of osmotic cathartic agents (e.g. lactulose) Renal loss: Loop diuretics, osmotic diuresis (glucose, mannitol, urea), postobstructive diuresis, intrinsic renal disease Increased insensible loss: Fever, hyperventilation, mechanical ventilation Renal loss: Central or nephrogenic diabetes insipidus Hypervolemic hypernatremia (hypertonic sodium gain) Ingestion or administration of hypertonic sodium: Seawater, hypertonic NaHCO3, hypertonic NaCl, salt poisoning in infants (hypertonic feeding formula), hypertonic saline enema Endocrine disorders: Cushing s syndrome, primary hyperaldosteronism LANDSPITALI THE NATIONAL UNIVERSITY HOSPITAL OF ICELAND DIVISION OF NEPHROLOGY

29 Evaluation of hypernatremia Look for a source of water loss Determine volume status Measure blood glucose Measure urine Na + and osmolality Urinary osmolality (mosm/l): >500 < Exrarenal water loss or osmotic diuresis Impaired vasopressin secretion or response to vasopressin Nonspecific LANDSPITALI THE NATIONAL UNIVERSITY HOSPITAL OF ICELAND DIVISION OF NEPHROLOGY

30 Calculation of water deficit in a patient with hypernatremia Volume of distribution is total body water (TBW) Water deficit = normal body water (NBW) current body water (CBW) Assuming pure water loss CBW x SNa + = NBW x 140 NBW = CBW x SNa TBW calculated as fraction of body weight: Men 0.6 Elderly men 0.5 Women 0.5 Elderly women 0.45 Water deficit = (CBW x SNa + ) CBW 140 Water deficit = CBW x (SNa + 1) 140 LANDSPITALI THE NATIONAL UNIVERSITY HOSPITAL OF ICELAND DIVISION OF NEPHROLOGY

31 Treatment of symptomatic hypernatremia Rate of SNa + correction: 1-2 mmol/l/hr if severe manifestations 0.5 mmol/l if asymptomatic Initial volume replacement with intravenous 0.9% NaCl in patients with significant volume depletion Free water deficit replacement using intravenous 5% D5W or other hypotonic solutions (e.g. 0.45% NaCl) and/or enteral water Replace 50% of the water deficit over hours Replace the remainder of the deficit over the next hours Closely monitor SNa + LANDSPITALI THE NATIONAL UNIVERSITY HOSPITAL OF ICELAND DIVISION OF NEPHROLOGY

32 Sodium content and distribution of common infusion solutions Infusate Infusate Na + (mmol/l) Extracellular fluid distribution (%) 5% Dextrose in water % NaCl in 5% dextrose in water % NaCl in water Ringer s lactate % NaCl in water Adrogué & Madias, N Engl J Med 2000;342: LANDSPITALI THE NATIONAL UNIVERSITY HOSPITAL OF ICELAND DIVISION OF NEPHROLOGY

33 Treatment of underlying disorders Central diabetes insipidus Desmopressin nasal spray Nephrogenic diabetes insipidus Dietary solute restriction Thiazide diuretic NSAID Amiloride for lithium-induced NDI Primary polydipsia No specific treatment available Discontinue medications that exacerbate thirst LANDSPITALI THE NATIONAL UNIVERSITY HOSPITAL OF ICELAND DIVISION OF NEPHROLOGY

34 Thank you!

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