DIAGNOSIS AND MANAGEMENT of

A clinical Practice tool

HYPonAtReMiA

Section 1Severe Symptomatic Hyponatremia

A Medical emergency that Requires Prompt correction

• Severe neurologic symptoms

— Serum [sodium] typically < 120 mEq/L

— Seizures

— Decreased consciousness

— Coma

• Management

— Increase serum [sodium] by 4-6 mEq/L, which should reverse most manifestations

— Treatment: 100 mL bolus of 3% saline, repeated up to 3 times if necessary

Section 2Major considerations for Management of Hyponatremia

• Treat underlying condition(s) that precipitated development of hyponatremia

• Patients with chronic hyponatremia are more susceptible to complications of overcorrection

• Presence of end-stage renal disease, chronic kidney disease, and severe acute kidney injury?

– In these cases the serum osmolality, urine osmolality, and urine sodium concentration may not hold the same meaning in terms of workup

– Consult nephrologist for workup and dialysis

Section 3Management of excessive correction of chronic Hyponatremia (> 0.5 meq/L/hr)Lower Serum Sodium Concentration

• Cease all activities that would increase serum sodium concentration

— Rehydrate

— Replace water orally

• Infuse 5% dextrose in water: 3 mL/kg/hr

• Recheck serum [sodium] until goal is determined by optimal correction rate calculation

• If any concerns, CALL ICU or RENAL FOR HELP

Section 4 Hyponatremia

Severe [Na] <125 mEq/L; moderate [Na] 125-129 mEq/L; mild [Na] 130-135 mEq/L

ASSESS SERUM OSMOLALITYNormal serum osmolality

~280 mOsmLow serum osmolality

< 280 mOsmHigh serum osmolality

>280 mOsm

PseudohyponatremiaHypertriglyceridemia, hyperglobulinemia, etc.

Hypotonic hyponatremiaInability of kidneys to dilute urine?

HyperglycemiaAlso maltose, mannitol, radiocontrast,

uremic toxin buildup

Hypovolemic hyponatremiaTotal body water ↓

Total body sodium ↓↓

Euvolemic hyponatremiaTotal body water ↑

Total body sodium ↔

Hypervolemic hyponatremiaTotal body water ↑↑Total body sodium ↑

Urine osmolality > 450 mOsm/kg

Urine [Na] < 20 mEq/L

CAUSESExtrarenal lossVomitingDiarrheaSweatingFluid in burns Trauma

Urine [Na] > 20 mEq/L

CAUSESDiuretic renal loss(HCTZ and K sparing diuretic)Aldo deficiency(ACEI and spironolac- tone)Salt losing nephropathyBicarbonaturia(Acetazolamide-oral)Cerebral salt wastingKetonuria

Uos >SosmUrine [Na] >

20 mEq/L

CAUSESGlucocort deficiencyHypothyroidismStressCNS infectionBrain tumorRenal failureSIADH (refer to section 6 for list of meds for drug induced SIADH)

Uos < SosmUrine [Na] <

20 mEq/L

CAUSESPsychogenic polydipsiaLow solute intakeBeer potomaniaRenal failure

Urine osmolality > Sosm

Urine [Na] < 20 mEq/L

CAUSESHeart failureCirrhosisLow effective blood volumeRenal failureAnaphylaxis Sepsis

Urine [Na] > 20 mEq/L

CAUSESRenal failurePregnancy

TREATMENTOptimally manage underlying diseaseChronic: fluid restrictionAcute: NaCl + loop diureticAlternative use of vaptan in select cases with attention to liver function

If refractory to conservative treatment consider ICU admissionIf renal failure consider dialysis

Symptomatic

Acute < 48 hours Chronic > 48 hours

Urgent need of treatmentTREATMENTConsider stopping offending meds (refer to section 6)Consider withholding meds until hyponatremia resolves3% NaCl 1-2 mL/kg/hr until symptoms subside and then water restriction + 3%NaCl + loop diuretic

Calculated to achieve target rate of correction Consider dialysis and/or reversing hemodynamic kidney disease with selected interventions

K repletion if needed

TREATMENTNo urgent need to treatStop offending meds (refer to section 6)Slow 3% NaCl Calculated to achieve target rate of correctionWater restriction + 3% NaCl + loop diuretic

Consider dialysis or continuous renal replacement therapy

K repletion if needed

Asymptomatic

TREATMENTNo immediate need to treatLong-term management Water restricition Furosemide + 2-3 g NaCl dailyAlternative use of vaptan in select cases with attention to liver function High protein diet

ASSESS VOLUME STATUS

ASSESS URINE [Na]; URINE OSMOLALITY

ASSESS NEUROLOGIC STATUS

Adapted from: Thompson C et al. Best Pract Res Clin Endocrinol Metab. 2012;26:S7-S15 and Verbalis JG et al. Am J Med. 2013;126:S1-S42

TREATMENTChronic: 0.9% NaClAcute: consider 3% NaCl

If refractory to conservative treatment consider ICU admissionIf renal failure consider dialysis

TREATMENT Fluid Restriction

Section 5 Sodium Replacement calculation

Reference Information Regarding Correction of Hyponatremia with Saline Solutions

3% saline = 513 meq/L; normal saline = 154 meq/L

Body water (L/kg) = children/nonelderly male 0.6; nonelderly female/elderly male 0.5; elderly female 0.45

total body water = body water x weight (kg)

Recommended rate of correction: 10 meq/L on day 1; 8 meq/L on day 2

Maximum correction rate

normal risk 10 meq/L on day one; total of 18 meq/L after 2 days

High risk (chronic, asymptomatic) 8 meq/L in any 24-hour period

CASE EXAMPLE: USE OF 3% SALINE

Elderly female Body weight 50 kg Serum [Na] 112 mEq/L

Change in serum sodium caused by 1 Liter of 3% saline Change = infusate [Na] – serum [Na] Total body water + 1

= 513 – 112 = 401 = 17.1 mEq/L (0.45 x 50) +1 23.5

Maximum infusate in first 24 hrs desired change of 10 mEq/L = 17.1 mEq = 10 mEq 1,000 mL x 17.1 x = 10,000 mL x = 585 mL

Maximum infusate in second 24 hrs desired change of 8 mEq/L = 17. 1 mEq = 8 mEq 1,000 mL x 17.1 x = 8,000 mL x = 468 mL

Elderly female Body weight 50 kg Serum [Na] 112 mEq/L

Change in serum sodium caused by 1 Liter of NORMAL saline Change = infusate [Na] – serum [Na] Total body water + 1

= 154 – 112 = 42 = 1.79 mEq/L (0.45 x 50) +1 23.5

Maximum infusate in first 24 hrs desired change of 10 mEq/L = 1.79 mEq = 10 mEq 1,000 mL x 1.79 x = 10,000 mL x = 5,587 mL

Maximum infusate in second 24 hrs desired change of 8 mEq/L = 1.79 mEq = 8 mEq 1,000 mL x 1.79 x = 8,000 mL x = 4,469 mL

CASE EXAMPLE: USE OF NORMAL (0.9%) SALINE

Adapted from Androgue HS, Madias NE. N Engl J Med. 2000; 242:1581-1589

Diuretics• Indapamide• Thiazides• Furosemide • Aldosterone inhibitors

AVP Analogues• Desmopressin• Oxytocin

Antiepileptics• Carbamazepine• Oxcarbazepine• Sodium valproate• Lamotrigine• Levetiracetam

Antidepressants• Selective serotonin uptake inhibitors• Monoamine oxidase inhibitors• Tricyclics

Antipsychotics• Carbamazepine• Clozapine • Thioridazine• Trifl uoperazine• Haloperidol

Antiarrhythmic drugs• Amiodarone• Lorcainide • Propafenone

Anti-infectives• Azithromycin• Lopinavir• Miconazole• Rifabutin

Antiparkinson agents• Amantadine• Levodopa• Pramipexole• Trihexyphenidyl

Antineoplastics• Vinca alkaloids – Carboplatin – Cisplatin • Alkylating agents – Cyclophosphamide – Melphalan – Methotrexate – Ifosfamide

ACE inhibitors• Enalapril• Captopril

Pain medications• Opiates• Tramadol• COX-2 inhibitors• NSAIDS

Proton pump inhibitors• Omeprazole• Pantoprazole

Hypnotics• Temazepam

Hypoglycemic agents• Sulfonylureas

Street drugs• MDMA (ecstasy)• Nicotine

Section 6 Drugs that induce SiADH

Adapted from Liamis G et al. Am J Kidney Dis. 2008;52:144-153

This activity is supported by an educational grant from Otsuka America Pharmaceutical, Inc.

This tool guide is meant to be used in conjunction with proper supervision from appropriate clinical services.

The opinions expressed herein are those of the authors and do not necessarily represent the views of Albert Einstein College of Medicine, Montefi ore Medical Center, Rockpointe or Otsuka, USA. Please review complete prescribing information of specifi c drugs or combination of drugs, including indications, contraindications, warnings, and adverse effects before administering pharmacologic therapy to patients.

This reference tool is a companion to “HYPONATREMIA: Detection and Management in the Hospital Setting” a CME-certifi ed program jointly provided by Albert Einstein College of Medicine of Yeshiva University and Montefi ore Medical Center’s Center for Continuing Medical Education and Rockpointe.

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