Diagnosis and Treatment of Hyponatremia

Diagnosis and Treatment of Hyponatremia

Acute: SymptomaticChronic: Asymptomatic

Thomas DuBose,M.D.Professor and Chair, Internal

MedicineWake Forest University School of

Medicine

Hyponatremia: ICUHyponatremia: ICU Pseudohyponatremia

• 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

Major Causes of Hyponatremia

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.

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

Estimating the Serum Osmolality

Estimating the Serum Osmolality

In Spurious Hyponatremia:

Calculated OSMp < Determined OSMp

Spurious Hyponatremia (hyperlipemia, hyperproteinemia) is not a hypoosmolar state.

2[Na]p BUN

2.8 GLUCOSE

18

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

Antidiuretic DrugsAntidiuretic DrugsAntidiuretic hormones:Antidiuretic hormones: Vasopression

OxytocinDiuretics:Diuretics: Thiazides

FurosemideEthacrynic acid

CNS-active drugs:CNS-active drugs: VincristineCarbamazepinePsychotropic drugs

Inhibitors of prostaglandin synthesis:Inhibitors of prostaglandin synthesis: ChlorpropamideSalicylatesAcetaminophenNonsteroidal anti-inflammatory agentsCOX 2 inhibitors

Others:Others: ClofibrateCyclophosphamideSomatostatinEcstasy

Syndrome of Inappropriate ADH Release (Bartter’s

Criteria)

Syndrome of Inappropriate ADH Release (Bartter’s

Criteria)Hyponatremia and true hypoosmolality by

definitionEuvolemia clinicalUrine less than maximally dilute (urinary

osmolality usually > 200 mOsm/kg of H2O)Normal renal, cardiac, hepatic, adrenal,

pituitary, and thyroid functionNo history of antidiuretic drugsNo emotional or physical stressUrinary sodium > 20 mEq/litera

a Urinary sodium may be <20 mEq/liter if the patient is volume

deleted or on low sodium intake.

Disorders Associated With SIADH

Disorders Associated With SIADH

Carcinomas

Pulmonary disorders

Central nervous system disorders

Most Common Causes of SIADH in Elderly (CDP and

NHR)*

Most Common Causes of SIADH in Elderly (CDP and

NHR)*

MedicationsIdiopathic formMalignancies

*Aging Clin Exp Res 2003, 15:6-11.

Small cell carcinoma of the lungCarcinoma of the duodenumCarcinoma of the pancreasThymomaLymphomaEwing’s sarcomaMesotheliomaCarcinoma of the bladderProstatic carcinomaOlfactory neuroblastoma

Disorders Associated With SIADH: Carcinomas

Disorders Associated With SIADH: Carcinomas

Disorders Associated With SIADH: Pulmonary

Disorders

Disorders Associated With SIADH: Pulmonary

DisordersViral pneumoniaBacterial pneumoniaPulmonary abscessTuberculosisAspergillosisPositive-pressure breathingAsthmaPneumothoraxCystic fibrosisLung cancers

Disorders Associated With SIADH: Central Nervous

Disorders

Disorders Associated With SIADH: Central Nervous

DisordersEncephalitis (viral or

bacterialMeningitis (viral,

bacterial, tuberculosis, fungal)

Head traumaBrain abscessBrain tumorsGuillain-Barré syndromeAcute intermittent

porphyriaSubarachnoid

hemorrhage or subdural hematoma

Cerebellar and cerebral atrophy

Cavernous sinus thrombosis

Neonatal hypoxiaHydrocephalusShy-Drager syndromeRocky Mountain spotted

feverDelirium tremensCerebrovascular accident

(cerebral thrombosis or hemorrhage)

Acute psychosisPeripheral neuropathyMultiple sclerosis

Guiding Principles in the Treatment of Hyponatremia

Guiding Principles in the Treatment of Hyponatremia1. 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.

A Prudent Approach to the Treatment of Hyponatremia

- 1

A Prudent Approach to the Treatment of Hyponatremia

- 1Acute Symptomatic Hyponatremia (duration <

48 hours)

1. Risk for complication of cerebral edema greater than risk of treatment of complication.

2. Treat with hypertonic NaCl: 3% NaCl @ 1-2 mL/kg/hr or 2 mEq/L/hr. until convulsions subside. Usually means increasing [Na+] by 10%.

3. Alternative: furosemide and hypertonic NaCl

4. Full correction is dangerous. Correct by 10% or to 120-122 mEq/L slowly.

5. Then initiate water restriction.

A Prudent Approach to the Treatment of Hyponatremia

- 2

A Prudent Approach to the Treatment of Hyponatremia

- 2Symptomatic 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 300 - 600 mg bid• V2 receptor antagonist? Aquaretics

Therapeutic Strategy Based On

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

A Prudent Approach to the Treatment of Hyponatremia

- 3

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.

Calculating Sodium Requirement in Hyponatremia

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 LBody water in abnormal state = (x) (120) = (42)(140) =

49LExcess 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.

How to predict the effect of therapy on the patient’s serum

sodium

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

[Na]Patient

[Na ]Bot [Na ]Patient

TBW 1

Diagnosis and Treatment of

Hypernatremia

Diagnosis and Treatment of

Hypernatremia

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

Causes of HypernatremiaCauses 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

Alcohol Diphenylhydantoin Lithium Demeclocycline Acetohexamde Tolazamide

Glyburide Propoxyphene Amphotericin Methoxyflurane Norepinephrine

Diuretic DrugsDiuretic Drugs

Patient Groups at Increased Risk for

Hypernatremia

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

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

Therapeutic Regimens for the Treatment of Diabetes

Insipidus

Therapeutic Regimens for the Treatment of Diabetes

Insipidus Drug Dose

Complete central diabetes insipidus

dDAVP 10-20 mg intranasally q 12-24 hr

Vasopressin tannate

2-5 U IM q 24-48 hr

Aqueous vasopressin

5-10 U SQ q 4-6 hr

Chlorpropamide 250-500 mg/ day

Clofibrate 500 mg tid-qid

Partial central diabetes insipidus

Carbamazepine 400-600 mg/ day

Thiazide diuretics

Conventional doses

NSAIDS Conventional doses

Nephrogenic diabetes insipidus (NDI)

Amiloride (for lithium-related NDI)

5 mg qd

Nephrogenic Diabetes Insipidus

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

Treatment of Symptomatic Hypernatremia

Treatment of Symptomatic Hypernatremia

1.Drop Na+S by 2 mEq/L/hr.

2.Replace 50% of water deficit over 12-24 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.