Evolving Strategies for Hyponatremia Management in the ICU

Mazen Kherallah, MD, FCCPInfectious Disease & Critical Care MedicineAssistant 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

Anderson1 Terzian2 Tierney30%

5%

10%

15%

20%

25%

[Na+] <130 mEq/L Normonatremia

1. Anderson RJ et al. An Intern Med. 1995,102: 164-1682. Terzian C et al. J Gen Intern Md. 1994,9:89-913. Tierney WM et al. J Gen Intern Med. 1986;1: 380-385

Morbidities in Hospitalized Patients with Symptomatic Hyponatremia

0%10%20%30%40%50%60% Altered

Sensorium

Seizures

Nausea & Vomiting

Gait Dis-turbance &

Falls Dysarthria Coma

• 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+]=

Brain CT Scan: Cerebral Edema

Normal CT ScanFatal

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 UrineNa 116 mEq/L Na 35 mEq/LK 3.9 mEq/L K 15 mEq/LCreat 0.8 mg/dL Osm 92 mOsm/kgOsm 240 mOsm/kg

Question

What is the most likely etiology of this man’s hyponatremia?a) Syndrome of inappropriate antidiuresisb) Psychogenic polydipsiac) Pseudohyponatremiad) Adrenal insufficiencye) 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

HypovolemiaAppropriate ADH Secretion

EuvolemiaInappropriate ADH

HypervolemiaMaladaptive 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 LossesDiuretic excessMineralocorticoid deficiencyBicarbonaturia with tubal acidosis and metabolic alkalosisKetonuriaOsmotic diuresis

Extrarenal lossesVomitingDiarrheaThird spacing of fluidsBurnsPancreatitisTrauma

Glucocorticoid deficiencyHypothyroidismSyndrome of inappropriate ADH secretion

Acute or chronic renal failure

Nephrotic syndromeCirrhosisCardiac failure

1. Is it real? Plasma Osmolality Normal or HighPseudohyponatremiaHyperglycemiaAzotemia, 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 UrineNa 126 mEq/L Na 45 mEq/LK 3.6 mEq/L K 17 mEq/LCreat 0.7 mg/dL Osm 292 mOsm/kgOsm 258 mOsm/kg

Question

What is the most likely etiology of this patient’s hyponatremia?a) SIADHb) Psychogenic polydipsiac) Pseudohyponatremiad) Adrenal insufficiencye) Cerebral sat wasting

Assessment of Hyponatremia:Three Critical Questions

HypovolemiaAppropriate ADH Secretion

EuvolemiaInappropriate ADH

HypervolemiaMaladaptive 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 LossesDiuretic excessMineralocorticoid deficiencyBicarbonaturia with tubal acidosis and metabolic alkalosisKetonuriaOsmotic diuresis

Extrarenal lossesVomitingDiarrheaThird spacing of fluidsBurnsPancreatitisTrauma

Glucocorticoid deficiencyHypothyroidismSyndrome of inappropriate ADH secretion

Acute or chronic renal failure

Nephrotic syndromeCirrhosisCardiac failure

1. Is it real? Plasma Osmolality Normal or HighPseudohyponatremiaHyperglycemiaAzotemia, 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 infusiond) 3% hypertonic salinee) IV Conivaptan

Treatment Considerations

• Often unknown• >2 days• Acute

reduction in chronic state

• More brain adaptation with chronicAcute 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 Symptom

s: Confusion

and/or lethargyMild 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 +0.2 111 132 -0.8 212 138 -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 EffectsV1a Vascular smooth muscle

cellsPlateletsLymphocytes and monocytesAdrenal cortex

VasoconstrictionPlatelet aggregationCoagulation factor releaseGlyconeogenesis

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 InjuryTherapeutic Options

Speed Situation Pluses MinusesFree 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 hypovolemiaElectrolyte depletion

Hypertonic saline

Fastest Symptomatic hyponatremia

Reduce brain edema

Fluid overload

Thank you