1. Diagnosis and Treatment of Hyponatremia
Acute: Symptomatic Chronic: Asymptomatic
Thomas DuBose,M.D.
Professor and Chair, Internal Medicine
Wake Forest University School of Medicine

5. Hyponatremia: ICU Pseudohyponatremia Post-operative Hyponatremia SIADH
Hyperglycemia, Hyperlipidemia
Post-operative Hyponatremia
SIADH
Cerebral Salt Wasting
Mechanical Ventilation
Cirrhosis
Congestive Heart Failure
SIRS/MODS
Loop diuretics with hypotonic fluid replacement
Certain drug intoxications
Agents that enhance ADH release or action

6. Major Causes of Hyponatremia
EIVF Depletion
True Volume Depletion
CHF or Cirrhosis
SIADH
Hormone mediated
Adrenal Insufficiency
Hypothyroidism
Pregnancy
Disorders in which ADH levels may be appropriately suppressed
Advanced renal failure
Primary polydipsia
Beer drinker’s potomania
Pseudohyponatremia
High plasma osmolality: hyperglycemia, mannitol, urea
Normal plasma osmolality: hyperlipidemia, hyperproteinemia, glycine infusion.

7. Steps in the Evaluation of Hyponatremia
Calculate plasma osmolality
Measure plasma osmolality
When low; defines true hypo-osmolal state or clinical hyponatremia
Consider plasma glucose, protein and lipids
Evaluate volume status of patient
Volume depletion
Volume expansion
Euvolemia
Measure urine sodium

8. Estimating the Serum Osmolality
In Spurious Hyponatremia:
Calculated OSMp < Determined OSMp
 Spurious Hyponatremia (hyperlipemia, hyperproteinemia) is not a hypoosmolar state.

9. Causes of Hypoosmolality
Volume Depletion
GI, lung or skin losses
Third space sequestration
Adrenal insufficiency
Renal salt wasting
Cerebral salt wasting
Volume Expansion
CHF, cirrhosis with ascites, nephrotic syndrome
Euvolemic
SIADH, water intoxication, reset osmostat, drugs

10. Antidiuretic Drugs Antidiuretic hormones: Vasopression Oxytocin
Diuretics: Thiazides
Furosemide
Ethacrynic acid
CNS-active drugs: Vincristine
Carbamazepine
Psychotropic drugs
Inhibitors of prostaglandin synthesis:
Chlorpropamide
Salicylates
Acetaminophen
Nonsteroidal anti-inflammatory agents
COX 2 inhibitors
Others: Clofibrate
Cyclophosphamide
Somatostatin
Ecstasy

11. Syndrome of Inappropriate ADH Release (Bartter’s Criteria)
Hyponatremia and true hypoosmolality by definition
Euvolemia clinical
Urine less than maximally dilute (urinary osmolality usually > 200 mOsm/kg of H2O)
Normal renal, cardiac, hepatic, adrenal, pituitary, and thyroid function
No history of antidiuretic drugs
No emotional or physical stress
Urinary sodium > 20 mEq/litera
a Urinary sodium may be <20 mEq/liter if the patient is volume deleted or on low sodium intake.

12. Disorders Associated With SIADH
Carcinomas
Pulmonary disorders
Central nervous system disorders

13. Most Common Causes of SIADH in Elderly (CDP and NHR)*
Medications
Idiopathic form
Malignancies
*Aging Clin Exp Res 2003, 15:6-11.

14. Disorders Associated With SIADH: Carcinomas
Small cell carcinoma of the lung
Carcinoma of the duodenum
Carcinoma of the pancreas
Thymoma
Lymphoma
Ewing’s sarcoma
Mesothelioma
Carcinoma of the bladder
Prostatic carcinoma
Olfactory neuroblastoma

15. Disorders Associated With SIADH: Pulmonary Disorders
Viral pneumonia
Bacterial pneumonia
Pulmonary abscess
Tuberculosis
Aspergillosis
Positive-pressure breathing
Asthma
Pneumothorax
Cystic fibrosis
Lung cancers

16. Disorders Associated With SIADH: Central Nervous Disorders
Encephalitis (viral or bacterial
Meningitis (viral, bacterial, tuberculosis, fungal)
Head trauma
Brain abscess
Brain tumors
Guillain-Barré syndrome
Acute intermittent porphyria
Subarachnoid hemorrhage or subdural hematoma
Cerebellar and cerebral atrophy
Cavernous sinus thrombosis
Neonatal hypoxia
Hydrocephalus
Shy-Drager syndrome
Rocky Mountain spotted fever
Delirium tremens
Cerebrovascular accident (cerebral thrombosis or hemorrhage)
Acute psychosis
Peripheral neuropathy
Multiple sclerosis

17. Guiding Principles in the Treatment of Hyponatremia
1. Neurologic disease can follow both the failure to promptly treat as well as injudiciously rapid treatment of hyponatremia.
2. Presence or absence of significant neurologic signs and symptoms must guide treatment.
3. Acuity or chronicity of the electrolyte disturbance impacts the rate at which the correction should be undertaken.

18. A Prudent Approach to the Treatment of Hyponatremia - 1
Acute Symptomatic Hyponatremia (duration < 48 hours)
Risk for complication of cerebral edema greater than risk of treatment of complication.
Treat with hypertonic NaCl: 3% 1-2 mL/kg/hr or 2 mEq/L/hr. until convulsions subside. Usually means increasing [Na+] by 10%.
Alternative: furosemide and hypertonic NaCl
Full correction is dangerous. Correct by 10% or to mEq/L slowly.
Then initiate water restriction.

19. A Prudent Approach to the Treatment of Hyponatremia - 2
Symptomatic Hyponatremia (Chronic or Unknown Duration)
1. Increase serum sodium by 10%, that is, approximately 10 mEq/L and then water restrict. Usually 1 -2 mL/kg/hr of hypertonic saline.
2. Do not exceed a correction rate of 1.5 mEq/L/hr at any given time.
3. Do not increase serum sodium by more than
15 mEq/day.
4. Long-term
H2O restriction
Demeclocycline mg bid
V2 receptor antagonist? Aquaretics

20. Therapeutic Strategy Based On
Volume Status of Patient
Presence of Absence of Symptoms
Duration of Hypoosmolality
Presence of absence of risk factors for development of neurological complication
Osmotic demyelination is rare in patients with initial Na+ > 120mEq/L

21. A Prudent Approach to the Treatment of Hyponatremia - 3
Asymptomatic Hyponatremia
1. Almost always chronic.
2. Treat with water restriction regardless of how low the serum sodium.

22. Calculating Sodium Requirement in Hyponatremia
In correcting hyponatremia the approximate expansion of total body water must be determined first by calculating the volume of water which was required to dilute the serum sodium concentration to its observed value. For example, in a 70 kg patient with a serum Na+ concentration of 120 mEq/L rather than 140 mEq/L, this calculation is made as follows:
Body water in normal state = (70 kg) (0.60) = 42 L
Body water in abnormal state = (x) (120) = (42)(140) = 49L
Excess body water = 7 L
The amount of Na+ in milliequivalents required for correction can then be calculated; again it is necessary to assume Na+ is distributed throughout the total body water.
(140-patient’s - Na+) (calculated total body water) = total Na+ requirement.

23. How to predict the effect of therapy on the patient’s serum sodium
The Bottle:
0.9% = 154 mEq/L
Ringer’s = 130 mEq/L
0.45% = 77 mEq/L
3% = 513 mEq/L

25. Diagnosis and Treatment of Hypernatremia

26. Steps in Evaluation of Hypernatremia
Establish history of water intake, and integrity of thirst mechanism
Severe hypernatremia is unusual unless thirst mechanism is defective or water is not available to the patient.
Determine patient’s volume status
Measure urine sodium concentration

27. Causes of Hypernatremia
Volume Depletion
Urine Na+ < 20: sweating, diarrhea, burns
Urine Na+ > 20: Renal losses: Hyperglycemia, mannitol, urea (osmotic diuresis), or intrinsic renal disease
Volume Expansion
Urine Na+ > 20: Salt loading, Cushing’s syndrome, NaHCO3, hypertonic dialysis
Eulovemic
Urine Na+ < 20: Fever, heat exhaustion, hypermetabolic state
Urine Na+ variable or > 20: Central DI, Nephrogenic DI

28. Diuretic Drugs Glyburide Propoxyphene Amphotericin Methoxyflurane
Alcohol
Diphenylhydantoin
Lithium
Demeclocycline
Acetohexamde
Tolazamide
Glyburide
Propoxyphene
Amphotericin
Methoxyflurane
Norepinephrine

29. Patient Groups at Increased Risk for Hypernatremia
Post craniotomy (sellar tumors)
Elderly, nursing home residents
Hypertonic infusions
Tube feedings
Osmotic diuretics
Lactulose
Mechanical ventilation
Diabetes mellitus with poor glycemic control
Polyuric disorders

30. Diabetes Insipidus Central DI Failure to synthesize or secrete ADH
Unable to concentrate urine with water deprivation (caution !)
3% decrease in BW or increase in Posm to 295 normally results in increase in Uosm > 700
Submaximal response: give ADH
Central DI Uosm will increase by 100% or more

31. Therapeutic Regimens for the Treatment of Diabetes Insipidus

32. Nephrogenic Diabetes Insipidus
Does not respond to AVP
Causes:
Congenital NDI - AVPR2 or AQP2 mutation
Hypokalemia
Hypercalcemia
Drugs: Lithium, demeclocycline, glyburide, colchicine, amphotericin B
Treatment:
Thiazides
Reduce solute intake (low Na+ diet)
NSAIDS

33. Treatment of Symptomatic Hypernatremia
1. Drop Na+S by 2 mEq/L/hr.
2. Replace 50% of water deficit over hrs.
3. Replace rest over next 24 hrs.
4. Perform serial neurological exams.
5. Decrease rate of correction when patient improved.
6. Measure Na+ in serum and urine q 12 hrs.