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

2. Not sponsored by any pharmaceutical companies
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. Initial Lab Results 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

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 
4/22
4/26
4/27 (a.m.)
4/27 (p.m.)
Na+
145
154
150 K
4.5
4.8
4.4 Cl
110
114
115
117
CO2 25 29 26
BUN 17 28 27
Creat
1.1
1.4
Glu 87
100 92

26. Formula for Managing Hypernatremia
CLINICAL USE
Estimate the effect of 1 liter of any infusate on serum Na+
Estimate the effect of 1 liter of any infusate containing Na+ and K+ 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+

27. Characteristics of Infusate
Infusate Na+
Extracellular-Fluid Distribution
mmol per liter %
5% Dextrose in H20 40
0.2% NaCl in 5% dextrose in H2O 34 55
0.45% NaCl in H2O 77 73
Ringer’s lactate
130 97
0.9% NaCl in H2O
154
100

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 
4/22
4/26
4/27 (a.m.)
4/27 (p.m.)
4/28 (a.m.)
4/28 (p.m.)
Na+
145
154
150
151
148 K
4.5
4.8
4.4
4.2
3.7 Cl
110
114
115
117
CO2 25 29 26
BUN 17 28 27 23 20
Creat
1.1
1.4
1.3
Glu 87
100 92

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