Evolving Strategies for Hyponatremia

Management in the ICU

Mazen Kherallah, MD, FCCP Infectious Disease & Critical Care Medicine

Assistant Professor, University of North Dakota

Critical Care Patients at Increased Risk of

Hyponatremia*

Increased age1

Up to 30% of patients with subarachnoid hemorrhage2

Up to 30% of ICU patients3

Over 30% of AIDS patients4

Postoperative patients

– 25%-35% of pituitary surgery for tumor resection5

~30% of acute spinal cord injury6

Psychiatric inpatients: 6%-17%7

*Data not exclusive to patients with euvolemic hyponatremia.

1. Hawkins RC. Clin Chim Acta. 2003;337:169-172; 2. Mayer SA. The Neurologist. 1995;1:71-85;

3. DeVita MV et al. Clin Nephrol. 1990;34:163-166; 4. Tang WW et al. Am J Med. 1993;94:169-174;

5. Bhardwaj A. Ann Neurol. 2006;59:229-236; 6. Peruzzi WT et al. Crit Care Med. 1994;22:252-258;

7. Siegler EL et al. Arch Intern Med. 1995;155:953-957.

Mortality Related to Hyponatremia Among

Hospitalized Patients

0%

5%

10%

15%

20%

25%

Anderson1 Terzian2 Tierney3

[Na+] <130 mEq/L Normonatremia

1. Anderson RJ et al. An Intern Med. 1995,102: 164-168

2. Terzian C et al. J Gen Intern Md. 1994,9:89-91

3. Tierney WM et al. J Gen Intern Med. 1986;1: 380-385

Morbidities in Hospitalized Patients with

Symptomatic Hyponatremia

Altered

Sensorium

Seizures

Nausea &

Vomiting Gait Disturbance

& Falls Dysarthria Coma

0%

10%

20%

30%

40%

50%

60%

• Single center, retrospective over 4 years (1997-2001)

• 168 patients with serum [Na+] <115 mEq/L

• Symptoms of hyponatremic encephalopathy in 89 of 168 patient (53%)

• No documented symptoms in 79 of 168 patients (47%)

Nzenue CM et al. J Natl Med Assoc. 2003;95: 335-343

Mechanisms of Hyponatremia

↓[Na+]=𝑁𝑎

↑𝐻2𝑂 ↓[Na+]=

↓𝑁𝑎

𝐻2𝑂

Brain CT Scan: Cerebral Edema

Normal CT Scan Fatal Hyponatremia

Case I

44 year old man with schizophrenia is brought to the ED from his group home after

a witnessed tonic-clonic generalized seizure.

He was well until earlier in the day at which time he became progressively

somnolent.

His medications include haloperidol, quetiapine and citalopram.

On exam he is afebrile, BP 120/78, HR 92. He is somnolent but arousable and

following commands, is euvolemic, and there are no focal findings.

His urine output is 120 ml/hour

Serum Urine

Na 116 mEq/L Na 35 mEq/L

K 3.9 mEq/L K 15 mEq/L

Creat 0.8 mg/dL Osm 92 mOsm/kg

Osm 240 mOsm/kg

Question

What is the most likely etiology of this man’s

hyponatremia?

a) Syndrome of inappropriate antidiuresis

b) Psychogenic polydipsia

c) Pseudohyponatremia

d) Adrenal insufficiency

e) Cerebral sat wasting

The Diagnosis of Hyponatremia: Three Critical Questions

Is it real? Is water excretion

appropriate? Is ADH excretion “appropriate”?

Assessment of Hyponatremia: Three Critical Questions

Hypovolemia Appropriate ADH Secretion

Euvolemia Inappropriate ADH

Hypervolemia Maladaptive ADH Secretion

Total body water ↓

Total body Na+ ↓↓

Total body water ↑

Total body Na+ ↔

Total body water ↑↑

Total body Na+↑

U[Na+] >20 mEq/L U[Na+] <20 mEq/L U[Na+] >20 mEq/L U[Na+] >20 mEq/L U[Na+] 20 <mEq/L

Renal Losses

Diuretic excess

Mineralocorticoid

deficiency

Bicarbonaturia with

tubal acidosis and

metabolic alkalosis

Ketonuria

Osmotic diuresis

Extrarenal losses

Vomiting

Diarrhea

Third spacing of

fluids

Burns

Pancreatitis

Trauma

Glucocorticoid deficiency

Hypothyroidism

Syndrome of inappropriate

ADH secretion

Acute or chronic

renal failure

Nephrotic syndrome

Cirrhosis

Cardiac failure

1. Is it real? Plasma Osmolality Normal or High Pseudohyponatremia

Hyperglycemia

Azotemia, ETOH Intoxication

Low

2. Is water excretion appropriate? Urine Osmolality Low

(< 100 mOsm/kg) Psychogenic polydipsia

High (>100 mOsm/kg)

3. Is ADH secretion appropriate? (Volume Status)

240 mOsm/kg

92 mOsm/kg

Case II

46-year-old woman admitted to

Neurocritical Care Unit confused and

mildly lethargic secondary to subarachnoid

hemorrhage

Past medical history: hypertension, tobacco

smoker

BP 170/78 mm Hg, HR 71 bpm

0.9% saline administered at 100 mL/h

CVP 6-8 mm Hg

Mildly positive fluid balance

Remained confused and disoriented, but

lethargy gradually resolved

In the Step-Down Unit

Day 9 post-SAH

Patient transferred to step-down unit

Central venous IV catheter discontinued

IV fluid: normal saline administered at 100 mL/h through peripheral IV

Day 10 post-SAH

The patient appeared to be more confused

Serum [Na+] = 126 mEq/L

Serum Urine

Na 126 mEq/L Na 45 mEq/L

K 3.6 mEq/L K 17 mEq/L

Creat 0.7 mg/dL Osm 292 mOsm/kg

Osm 258 mOsm/kg

Question

What is the most likely etiology of this patient’s

hyponatremia?

a) SIADH

b) Psychogenic polydipsia

c) Pseudohyponatremia

d) Adrenal insufficiency

e) Cerebral sat wasting

Assessment of Hyponatremia: Three Critical Questions

Hypovolemia Appropriate ADH Secretion

Euvolemia Inappropriate ADH

Hypervolemia Maladaptive ADH Secretion

Total body water ↓

Total body Na+ ↓↓

Total body water ↑

Total body Na+ ↔

Total body water ↑↑

Total body Na+↑

U[Na+] >20 mEq/L U[Na+] <20 mEq/L U[Na+] >20 mEq/L U[Na+] >20 mEq/L U[Na+] 20 <mEq/L

Renal Losses

Diuretic excess

Mineralocorticoid

deficiency

Bicarbonaturia with

tubal acidosis and

metabolic alkalosis

Ketonuria

Osmotic diuresis

Extrarenal losses

Vomiting

Diarrhea

Third spacing of

fluids

Burns

Pancreatitis

Trauma

Glucocorticoid deficiency

Hypothyroidism

Syndrome of inappropriate

ADH secretion

Acute or chronic

renal failure

Nephrotic syndrome

Cirrhosis

Cardiac failure

1. Is it real? Plasma Osmolality Normal or High Pseudohyponatremia

Hyperglycemia

Azotemia, ETOH Intoxication

Low

2. Is water excretion appropriate? Urine Osmolality Low

(< 100 mOsm/kg) Psychogenic polydipsia

High (>100 mOsm/kg)

3. Is ADH secretion appropriate? (Volume Status)

258 mOsm/kg

292 mOsm/kg

Question

How would you treat this patient?

a) Fluid restriction (<2 L/d)

b) Salt tablets (NaCl 2 g/d)

c) Normal saline infusion

d) 3% hypertonic saline

e) IV Conivaptan

Treatment Considerations

• Often unknown

• >2 days

• Acute reduction in chronic state

• More brain adaptation with chronic

Acute or Chronic

• Mild: >129

• Moderate: 121-129

• Severe <120

Severity of Hyponatremia

• Severe Symptoms or Intracranial Pathology: seizures, impaired mental status or coma

• Moderate: confusion, lethargy,

• Mild: fatigue, nausea, dizziness, gait disturbances, forgetfulness nd muscle cramps

• Asymptomatic

Severity of Symptoms

• Treat cerebral edema

• Relieve symptoms and prevent progression of neurologic dysfunction

• Prevent osmotic demyelination syndrome

• 4-6 meq/24 hrs (<9 meq/L in any 24 hrs)

Treatment Goals

Treatment Strategies

• Treat pain, nausea, vomiting,..

• cessation of therapy with certain drugs

• glucocorticoids to patients with adrenal insufficiency

Treat Underlying Cause

• Saline to patients with true volume depletion

• Diuretics in edematous states (such as heart failure and cirrhosis)

Restoration of Euvolemia

•Fluid restriction in SIADH

Balancing the Effect of ADH

• Hypertonic saline

• Normal saline

• Salt tablets

Correction of Na and Rate of Correction

Sodium deficit= TBW (desired SNa-actual SNa)

Increase in SNa= (infusate [Na]-SNa) ÷ (TBW+1)

Treatment Options

• (NS in hypovolemia)

• Fluid restriction (<UO or <800 ml/day)

• Salt tablets

• V2 receptors antagonists

• (NS in hypovolemia)

• Hypertonic saline

• Increase Na 0.5-1 meq/hour in the first 4 hours

• 4-6 meq in 24 hours

• Hypertonic saline

• Increase Na 0.5-1 meq/hour in the first 4 hours

• 4-6 meq in 24 hours (<9 meqin any 24 hours)

• Rapid increase in Na 4-6 meq/L (in 6 hours)

• 3% saline 100 mL IV bolus

• Repeat 1-2 X at 10 minutes intervals if symptoms persist

• ≤ 9 meq/L in 24 hours Severe

Symptoms: Seizure or

coma

Moderate Symptoms: Confusion

and/or lethargy

Mild or abscent

symptoms: Na > 120 meq/L

Mild or abscent

symptoms: Na ≤120 meq/L

Treatment Course for This Patient

A 20 mg loading dose of conivaptan followed by a continuous infusion of 20 mg/d

24 hour after the start of the loading dose, the serum [Na+]

increased from 126 to 132

A second 24 hour contineous infusion given

SAH

Day

Serum [Na+]

(mEq/L)

24 Hour Fluid

Balance (L)

Conivaptan

Treatment Day

10 126 +0.2 1

11 132 -0.8 2

12 138 -1.2 3

Day 2 of Treatment

The next day serum [Na+] increased from 132 to138 mEq/L

Mental status: less confused

Conivaptan discontinued

Patient discharged to rehabilitation on SAH Day 13

Receptor-Mediated Effects of VAP

Receptor Subtype Site of Action Activation Effects

V1a Vascular smooth muscle

cells

Platelets

Lymphocytes and

monocytes

Adrenal cortex

Vasoconstriction

Platelet aggregation

Coagulation factor release

Glyconeogenesis

V1b Anterior pituitary ACTH and ß-endorphin

release

V2 Renal collecting duct

principal cells

Free water absorption

Lee CR et al. AM Heart J. 2003;143:9-18

Hyponatremia in Acute Brain Injury

Therapeutic Options

Speed Situation Pluses Minuses

Free water

restriction

Slow Hard to

regulate

NS+furosemide Sow Electrolyte

depletion

Fludrocortisone Slow Fluid overload

AVP Inhibitor Faster Asymptomatic

hyponatremia

Reliable effect Infusion site

reactions

Mannitol Fatsest Symptomatic

hyponatremia

Reduce

Edema

Can worsen

hypovolemia

Electrolyte

depletion

Hypertonic

saline

Fastest Symptomatic

hyponatremia

Reduce brain

edema

Fluid overload

Thank you