CASE STUDY IN HYPONATREMIA

25th Annual Clinical Update in Geriatric Medicine Conference

DAVID J. LEVENSON MD

APRIL 6, 2017

CASE PRESENTATION

• YOUR MEDICAL ASSISTANT SENDS YOU THE FOLLOWING MESSAGE:

• “YOUR PATIENT JOAN SMITH, AGE 76, HAD LAB WORK DONE LAST WEEK.

• THE SERUM SODIUM IS 120 meq/L.”

WHAT COMES TO MIND?

• SIADH

• Cancer

• Psych meds

• Normal saline

• Tolvaptan

• CHF

• Head CT

• Osmotic demyelination

• Urea

• Urine osmolality

• 3% saline

• Hypothyroid

• Urine lytes

• Hyperosmolar

hyponatremia

• Central pontine myelinolysis

• Salt tablet

• Free water excretion

• Cirrhosis

• Thiazides

UNSPOKEN PHRASES

“WHY DOES IT HAVE TO BE SO COMPLICATED?”

“NORMAL SALINE”

“LET THE NEPHROLOGISTS DEAL WITH IT.”

A SIMPLE APPROACH

1. What does the patient have?

2. Why does she have it? What is the DDX?

3. How bad is it?

4. What shall we do -

– Diagnostically?

– Therapeutically?

1. WHAT DOES SHE HAVE?

• HYPONATREMIA

• HYPOOSMOLAR (MEASURE IF NEEDED)

• THE RATIO OF SALT TO WATER IS LOW – EXCESS WATER BUT NORMAL SALT CONTENT

or

– GREATER EXCESS OF WATER THAN SALT

or

– GREATER DEFICIT OF SALT THAN WATER

• IMPAIRED WATER EXCRETION

2. WHY DOES SHE HAVE IMPAIRED WATER EXCRETION?

• CAUSES FOR IMPAIRED WATER EXCRETION – ADH (VASOPRESSIN)

– (LOW GFR)

IF KIDNEY FUNCTION IS NORMAL,

SHE MUST HAVE ADH EXCESS

SO… WHAT REGULATES ADH RELEASE?

HYPONATREMIA SUPPRESSES ADH RELEASE

HOW DO WE PROVE THAT ADH IS PRESENT?

NORMALLY: HYPONATREMIA =>AVP SUPPRESSION=> UOSM<100

VOLUME DISORDERS STIMULATE ADH RELEASE

HYPOTHALAMUS

POSTERIOR PITUITARY

IS A VOLUME DISORDER STIMULATING ADH RELEASE?

• IF YES, THE PRESENCE OF ADH IS APPROPRIATE FOR

THE SITUATION – FIXING THE VOLUME DISORDER MAY SOLVE THE

HYPONATREMIA PROBLEM

– DETERMINE IF VOLUME STATUS IS LOW OR HIGH, AND WHAT ELSE IS WRONG WITH THE SYSTEMIC HEMODYNAMICS;

• IF NO, THEN THE PRESENCE OF ADH IS NOT APPROPRIATE – i.e., VOLUME NORMAL, OSM NOT HIGH

– THIS IS SIADH

– (OR A FEW OTHER THINGS: • hypothyroid, cortisol deficiency, reset osmostat, malnutrition)

WHAT CAUSES SIADH?

• ABNORMAL STIMULI OF ADH RELEASE – PAIN, NAUSEA, ANXIETY, – MEDS – CNS DISEASE – LUNG DISEASE

• ECTOPIC ADH PRODUCTION – CANCER - Lung, small intestine, pancreas, brain, etc.

• INCREASED RENAL SENSITIVITY TO ADH – NSAID, OTHER MEDS

• OTHER – HIV – Etc.

3. HOW BAD IS IT? THREE CRITERIA

• ABSOLUTE SODIUM LEVEL

– COMMON THRESHOLD: Na <120 MEQ/L

• NEUROLOGIC STATUS

– ABNORMAL MENTAL STATUS

– NEUROLOGIC DEFICITS

– SEIZURES, COMA

– CEREBRAL EDEMA

• ACUTE (24 HR) vs. CHRONIC

LOW [Na]

LOW [Na]

3. HOW BAD IS IT? THREE CRITERIA

• ABSOLUTE SODIUM LEVEL

– COMMON THRESHOLD: Na <120 MEQ/L

• NEUROLOGIC STATUS

– ABNORMAL MENTAL STATUS

– NEUROLOGIC DEFICITS

– SEIZURES, COMA

– CEREBRAL EDEMA

• ACUTE (24 HR) vs. CHRONIC

4. WHAT SHOULD WE DO - DIAGNOSTICALLY?

• ESTABLISH THE HISTORY

– MEDS, FLUID INTAKE, TIME COURSE

• IS VASOPRESSIN PRESENT?

• IS THERE A VOLUME DISORDER?

• WHAT IS THE NEUROLOGIC STATUS?

• IS THERE OTHER STUFF GOING ON?

– ACUTE ILLNESS, CANCER, ALCOHOLISM, MALNUTRITION, THYROID, ADRENAL DISEASE

4. WHAT SHOULD WE DO - DIAGNOSTICALLY?

• ESTABLISH THE HISTORY

– MEDS, TIME COURSE, FLUID INTAKE,

• IS VASOPRESSIN PRESENT? Uosm >100-150

• IS THERE A VOLUME DISORDER?

• WHAT IS THE NEUROLOGIC STATUS?

• IS THERE OTHER STUFF GOING ON?

– ACUTE ILLNESS, CANCER, ALCOHOLISM, MALNUTRITION, THYROID, ADRENAL DISEASE

4. WHAT SHOULD WE DO - DIAGNOSTICALLY?

• ESTABLISH THE HISTORY

– MEDS, TIME COURSE, FLUID INTAKE,

• IS VASOPRESSIN PRESENT? Uosm >100-150

• IS THERE A VOLUME DISORDER?

• WHAT IS THE NEUROLOGIC STATUS?

• IS THERE OTHER STUFF GOING ON?

– ACUTE ILLNESS, CANCER, ALCOHOLISM, MALNUTRITION, THYROID, ADRENAL DISEASE

IS THERE A VOLUME DISORDER?

• HISTORY:

– MEDS, WATER INTAKE, WEIGHT CHANGE,

• EXAMINATION

– ORTHOSTATIC SIGNS, SKIN TURGOR, AXILLARY SWEAT,

• LABS

– BUN/Cr ratio, UNa <20, FENa <1%,

– BNP, ALBUMIN, URIC ACID

4. WHAT SHOULD WE DO DIAGNOSTICALLY?

• ESTABLISH THE HISTORY

– MEDS, TIME COURSE, FLUID INTAKE,

• IS VASOPRESSIN PRESENT? Uosm >100-150

• IS THERE A VOLUME DISORDER?

• WHAT IS THE NEUROLOGIC STATUS? MSE!

• IS THERE OTHER STUFF GOING ON?

– ACUTE ILLNESS, CANCER, ALCOHOLISM, MALNUTRITION, THYROID, ADRENAL DISEASE

4. WHAT SHOULD WE DO DIAGNOSTICALLY?

• ESTABLISH THE HISTORY

– MEDS, TIME COURSE, FLUID INTAKE,

• IS VASOPRESSIN PRESENT? Uosm >100-150

• IS THERE A VOLUME DISORDER?

• WHAT IS THE NEUROLOGIC STATUS? MSE!

• IS THERE OTHER STUFF GOING ON?

– ACUTE ILLNESS, CANCER, ALCOHOLISM, MALNUTRITION, THYROID, ADRENAL DISEASE

MINIMUM ORDER SET

• ORTHOSTATIC SIGNS

• DAILY WEIGHT

• INTAKE AND OUTPUT

• URINE: LYTES, Cr, OSM, U/A

– BEFORE DIURETICS OR IV FLUIDS

• REPEAT BMP, THEN Q3-6H

• GLUCOSE

• REGULATE THE VOLUME OF FLUID INTAKE

4. WHAT SHOULD WE DO - THERAPEUTICALLY?

• GOALS: – RAISE SODIUM ENOUGH TO ELIMINATE THE RISK

OF NEUROLOGIC DYSFUNCTION AND BRAIN INJURY.

– AVOID RISK OF EXCESSIVELY RAPID CORRECTIOIN

• ISSUES: – HOW MUCH TO INCREASE THE SODIUM LEVEL?

– HOW FAST?

[[Na]

WHAT ARE THE RISKS AND DANGERS OF TREATMENT?

• UNDERTREATMENT – WORSENING HYPONATREMIA

• NEUROLOGIC DETERIORATION

• SEIZURE, COMA

• CEREBRAL EDEMA

• OVERTREATMENT – RAPIDLY RISING [Na+] > 8 MEQ/24H

• OSMOTIC DEMYELINATION SYNDROME

• “CENTRAL PONTINE MYELINOLYSIS”

• APPEARANCE MAY BE DELAYED BY DAYS

EMERGENCY SITUATIONS:

Na <120 and: • SEIZURES, COMA, HERNIATION, STROKE • ACUTE HYPONATREMIA (<24 HOURS) WITH SXS

– MARTHON RUNNERS – POST-OP – WATER INTOXICATION – ECSTASY (AMPHETAMINE) – CNS STRUCTURAL ANORMALITIES

GOAL of RX: RAISE Na by 4-6 meq QUICKLY – GIVE 100 CC OF 3% SALINE OVER 15 MINUTES, REPEAT prn. OTHERWISE: SLOW ONSET OF HYPONATREMIA-> SLOW CORRECTION

STANDARD OF PRACTICE

• DO NOT RAISE NA >8 MEQ IN ANY 24 HOUR PERIOD – ACTIVELY OR PASSIVELY!

• IF YOU DO , YOU MUST REVERSE COURSE AND CORRECT THE OVERSHOOT.

CAUTION

• SOME HYPONATREMIC PATIENTS WILL “AUTOCORRECT” SPONTANEOUSLY AND RAPIDLY, IF THE STIMULUS TO ADH ABATES:

– ACUTE PSYCHOSIS

– SEVERE VOLUME DEPLETION

– TRANSIENT SIADH

– THIAZIDE INDUCED

• THESE PATIENTS MAY REQUIRE VASOPRESSIN +/- D5W TO PREVENT OR REVERSE OVERCORRECTION.

• [Na] MUST BE MONITORED VERY CLOSELY

4. WHAT SHOULD WE DO - THERAPEUTICALLY?

• VOLUME DISORDERS – SALT DEFICIT: NS, 5% ALBUMIN, PRBCS

– SALT EXCESS: FLUID RESTRICTION, IV DIURETICS, INOTROPES, CARDIAC INTERVENTIONS, ?VAPTANS ETC.

• EUVOLEMIC = normal salt, excess water – STOP RELEVANT MEDS, e.g THIAZIDES

– FLUID RESTRICT

– ENHANCE WATER EXCRETION

– ALCOHOLISM, MALNUTRITION:

• INCREASE PROTEIN INTAKE

– ADDRESS DEFICIENCY OF T4, CORTISOL

WHAT’S WRONG WITH SALINE TO TREAT SIADH?

THEORY:

SALINE IS HYPEROSMOLAR VS PATIENT’S BLOOD

BUT:

• PATIENTS ARE EUVOLEMIC; THE SALT LOAD IS EXCRETED

• ADH LEVEL IS HIGH, SO THE WATER IS RETAINED

THE PATIENT WILL BECOME MORE HYPONATREMIC

NOT A SAFE OPTION!

4. WHAT SHOULD WE DO - THERAPEUTICALLY?

• VOLUME DISORDERS – DRY: NS, 5% ALBUMIN, PRBCS – VOLUME EXCESS: FLUID RESTRICTION, IV DIURETICS,

INOTROPES, CARDIAC INTERVENTIONS, ?VAPTANS ETC.

• EUVOLEMIC = normal salt, excess water – STOP RELEVANT MEDS, e.g THIAZIDES – FLUID RESTRICT – ENHANCE WATER EXCRETION – ALCOHOLISM, MALNUTRITION:

• INCREASE PROTEIN INTAKE – ADDRESS DEFICIENCY OF T4, CORTISOL – NO SALINE

THERAPY OF CHRONIC SIADH

GOAL: Na >120 and/or SX RESOLUTION

• ORAL FLUID RESTRICTION: 800-1500 CC/24H

• 3% SALINE 20-40CC/HR (IN ICU)

• SALT PILLS (NaCl 1 GM): 4-12/24H

• LASIX + SALT PILLS

• DEMECLOCYCLINE

• VAPTANS – IV: CONIVAPTAN – MUST INCREASE FLUID INTAKE AT

SAME TIME

– ORAL : TOLVAPTAN – LIMIT 30 DAYS

• ORAL UREA

TREATMENT: SUMMARY

1. TREAT BASED UPON THREE CRITERIA:

– ACUTE OR CHRONIC?

– SEVERE OR NOT?

– VOLUME DISORDER OR EUVOLEMIC?

2. EMERGENT SITUATIONS REQUIRE EMERGENT RX WITH CLOSE CONTINUOUS ICU MONITORING.

3. OVERCORRECTION (> 8 MEQ RISE/24 HRS) CARRIES THE RISK OF PERMANENT NEUROLOGIC INJURY AND DEATH, AND MUST BE REVERSED.

4. MOST CHRONIC HYPONATREMIA WITH Na >120 IS WELL TOLERATED, SO CORRECT SLOWLY.