Hypernatremia

1. Hypernatremia Primary Care Conference K. Mae Hla, M.D., M.H.S. April 21, 2004

2. Objectives • Brief review of pathophysiology, causes, clinical manifestations of hypernatremia • Review management, emphasizing a quantitative approach to correction of fluid imbalance Disclosure Not sponsored by any pharmaceutical companies

3. The Patient • 51-year-old male with acutely decompensated schizo-affective disorder was readmitted 1 day after discharge to UW Psychiatry involuntarily for increasing agitation and psychosis • History of noncompliance with medications (Lithium 1200 mg, Clozaril 375 mg, Modafinil 400 mg, Synthroid 75 mcg) all of which were restarted

4. Deterioration during hospitalization • Patient was in and out of locked seclusion due to violent behavior with subsequent poor oral intake • CBC, Chem 7 and CK were done after 4 days because staff felt that patient’s mental status has worsened and dystonia might be present • Serum sodium was noted to be high, and a general medicine consult was requested

5. Physical Exam • BP: 160/82, P: 92, T: 37; orthostatic to 110/60 previous evening per nursing note • Tongue and oral mucosa: dry • Skin: poor turgor and tenting • Cor: JVP-flat, normal heart sounds • Lungs: Clear. Abdomen, non-tender, BS + • GU: incontinent of urine in diaper • Neuro: limited exam, incoherent, psychotic, agitated, in 4 point leather restraints

6. Sodium = 154 Potassium = 4.4 Chloride = 115 HCO3 = 26 BUN = 27 Creatinine = 1.4 Calcium = 10.1 Glucose = 100 Urine Na+ = 41 Urine Osmolality = 492 Plasma Osmolality = 315 Initial Lab Results

7. What is the cause of his hypernatremia?

8. Water homeostasis • Water homeostasis is mediated by: • Thirst • Arginine Vasopressin (ADH) • Kidneys • A disruption in the water balance leads to abnormality in serum sodium

9. Hypernatremia (Na+> 145 mEq) • Hypernatremia is caused by a relative deficit of water in relation to sodium which can result from • Net water loss: accounts for majority of cases of hypernatremia • pure water loss • hypotonic fluid loss • Hypertonic gain results from iatrogenic sodium loading

10. Extracellular-Fluid & Intracellular-Fluid Compartments under Normal Conditions and during States of Hypernatremia

11. Causes of Hypernatremia Net water loss • Pure water loss • Unreplaced insensible losses (dermal and respiratory) • Hypodipsia • Neurogenic diabetes insipidus • Post-traumatic • tumors, cysts, histiocytosis, tuberculosis, sarcoidosis • Idiopathic • aneurysms, meningitis, encephalitis, Guillain-Barre´ syndrome

12. Pure Water Loss (cont’d) • Congenital nephrogenic diabetes insipidus • Acquired nephrogenic diabetes insipidus • Renal disease (e.g. medullary cystic disease) • Hypercalcemia or hypokalemia • Drugs (lithium, demeclocycline, foscarnet, methoxyflurane, amphotericin B, vasopressin V2-receptor antagonists)

13. Causes of Hypernatremia (cont’d) • Hypotonic fluid loss • Renal causes Loop diuretics Osmotic diuresis (glucose, urea, mannitol) Postobstructive diuresis Polyuric phase of acute tubular necrosis Intrinsic renal disease

14. Hypotonic Fluid Loss (cont’d) • Gastrointestinal causes Vomiting Nasogastric drainage Enterocutaneous fistula Diarrhea Use of osmotic cathartic agents (e.g., lactulose) • Cutaneous causes Burns Excessive sweating

15. Causes of Hypernatremia (cont’d) Hypertonic sodium gain Hypertonic sodium bicarbonate infusion Ingestion of sodium chloride Ingestion of sea water Sodium chloride-rich emetics Hypertonic saline enemas Intrauterine injection of hypertonic saline Hypertonic sodium chloride infusion Hypertonic dialysis Primary hyperaldosteronism Cushing’s syndrome

16. What is the hypernatremia due to in our patient? • Poor water/oral intake due to psychosis (per hx) • Acquired partial nephrogenic DI due to Lithium (suggested by low urine osmolality relative to high serum osmolality) • Increased insensible loss due to agitation, and hyperventilation • ?? Renal loss of sodium-urine Na+ 41

17. Clinical Manifestations • CNS dysfunction s/s depend on large or rapid increases in serum Na+ concentration • Outpatients: Affects extremes of ages • Infants: hyperpnea, restlessness, m/s weakness, lethargy, coma • Elderly: few sx until Na+ > 160; confusion, coma more related to coexisting condition • Inpatients: all ages, sx more elusive in presence of pre-existing neurologic dysfunction

18. Management A two-pronged approach: • Addressing the underlying cause: stopping GI loss, controlling pyrexia, hyperglycemia, correcting hypercalcemia or feeding preparation, moderating lithium induced polyuria • Correcting the prevailing hypertonicity: rate of correction depends on duration of hypernatremia to avoid cerebral edema

19. Effects of Hypernatremia on the Brain and Adaptive Responses

20. Correction of Hypernatremia • Hypernatremia that developed over a period of hours (accidental loading) • Rapid correction improves prognosis without cerebral edema • Accumulated electrolytes in brain rapidly extruded • Reducing Na+ by 1 mmol/L/hr appropriate

21. Rate of Correction (Cont’d) • Hypernatremia of prolonged or unknown duration • a slow pace of correction prudent • full dissipation of brain solutes occurs over several days • maximum rate 0.5 mmol/L/hr to prevent cerebral edema • A targeted fall in Na+ of 10 mmol/L/24 hr

22. Goal of Treatment • Reduce serum sodium concentration to 145 mmol/L • Make allowance for ongoing obligatory or incidental losses of hypotonic fluids that will aggravate the hypernatremia • In patients with seizures prompt anticonvulsant therapy and adequate ventilation

23. Administration of Fluids • Preferred route: oral or feeding tube • IV fluids if oral not feasible • Except in cases of frank circulatory compromise, isotonic saline is unsuitable • Only hypotonic fluids are appropriate-pure water, 5% dextrose, 0.2 % saline, 0.45% saline-the more hypotonic the infusate, the lower the infusion rate required

24. Calculation of Free Water Deficit Assuming pure water loss, CBW x [Na+] = NBW x 140 NBW = (CBW x [Na+]) / 140 Water deficit = NBW – CBW = {CBW x [Na+] / 140} – CBW = CBW {[Na+] / 140} – 1} = 65 x 0.6 x (154/140 – 1) = 39 x (14/140) = 3.9 L

25. Patient’s Serial Electrolytes Before and After Treatment  

26. CLINICAL USE Estimate the effect of 1 liter of any infusate on serum Na+ FORMULA* 1. Change in serum Na+ = 2. Change in serum Na+ = infusate Na+ - serum Na+ total body water + 1 (infusate Na+ + infusate K+) -serum Na+ total body water + 1 Estimate the effect of 1 liter of any infusate containing Na+ and K+ on serum Na+ Formula for Managing Hypernatremia

27. Characteristics of Infusate

28. Rate of infusion of 0.2 saline in 5% dextrose in water Change in Na+ with 1 L of above solution = (34-154) / {(65 x 0.6) + 1} = -120/40 = - 3 mEq/L Desired change in Na+ = 145 – 154 = - 9 mEq/L over 24 hours Thus needs 9/3 = 3 L (over 24 hours) Calculated rate of infusion = 3000/24 = 125 ml/hr

29. Change in Serum Na+ after adjusting the infusate and rate  

30. Summary of Managing Hypernatremia • Isotonic saline unsuitable except in ECF volume depletion causing hemodynamic instability • Switch to hypotonic solutions as soon as circulatory status stabilized • Avoid excessive rapid correction or over correction • Select the most hypotonic infusate suitable with appropriate allowances for ongoing fluid losses • Most important - reassess infusion prescriptions at regular intervals based on pt’s clinical status and electrolyte values