Sym pt om s of "hyponat rem ia" Serum [Na + ] m Eq/ L: - Asymptomatic

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1 Sym pt om s of "" Serum [Na + ] >130 m Eq/ L: - Asymptomatic Serum [Na + ] m Eq/ L: - Nausea, vomiting - Fatigue, muscle cramps - Abdominal symptoms - Mild cognitive - Gait disturbances Serum [Na + ] <125 m Eq/ L: - Headache - Agitation and confusion Serum [Na + ] <120 m Eq/ L: - Lethargy - Seizures and coma Effect s of rapidit y of developm ent Acut e - Serum is hypotonic relative to the brain. This osmotic gradient drives water into the brain. - Cerebral edema - CNS symptom Severe acut e - Brain damage - Brainstem herniation - Respiratory arrest - Rhabdomyolysis - Death Chronic - CNS adaptations occur (neurons decrease intracellular osmolality). - Cerebral edema, seizures, herniation are less frequent. Recognizes key diagnost ic clues Invest igat ion - Serum electrolytes Serum [Na + ] Hyponatremia (<135 meq/l) Significant hyponatremia (<130 meq/l) - Serum glucose - Serum BUN, creatinine - Serum and urine osmolarity St ep 1 (cont.) Assess t he pat ient 's serum osm olarit y Recent act ivit y - Recent marathon» exercised-associated hyponatremia (EAH) Drug - Thiazide use» diuretic-induced hyponatremia Know n underlying diseases - Heart failure - Liver or kidney disease - Volume loss, vomiting, diarrhea - Diabetes mellitus Know n abnorm al laborat ory values - Marked hyperglycemia - hyperglycemic-induced hyponatremia - Urine osmolarity <100 mosm/l - Psychogenic polydipsia - Ecstasy use - Beer potomania - Unexplained hyperkalemia - Kidney disease - Normal serum osmolarity - Pseudohyponatremia - Marked hyperlipidemia - Marked hypoproteinemia - Markedly elevated serum cretinine - Kidney disease

2 St ep 1 Assess t he pat ient 's serum osm olarit y (normal value mosm/kg) Low serum osm olarit y (<280 m Osm / kg) High serum osm olarit y (>295 m Osm / kg) Norm al serum osm olarit y ( m Osm / kg) Hypot onic (t rue ) Hypert onic (fact it ious ) - Hyperglycemia (1.6 meq/l for each rise of 100 mg/dl in serum glucose above 100 mg/dl) Drugs - Manitol, sorbitol, glycerol, maltose - Glycine (hyperglycinemia) - Radiocontrast agents Isot onic (pseudo) - Hypoproteinemia - Hyperlipidemia St ep 2 Assess t he pat ient 's volum e st at us using clinical and laboratory evidences Not e - Measuring serum [Na + ] and FeNa + are inaccurate and not necessary in evaluating hypervolemic hyponatremia - Hypotension, orthostatic changes Euvolem ic and subt le hypovolem ic - No clinical evidence of hypovolemia and hypervolemia (cont.) Assess t he pat ient 's serum [Na + ] - Serum [Na + ] <120 meq/l Then - Consult s nephrologist s Logics - Administering normal saline in patients with SIADH would increase aldosterone and ANP levels that facilitate sodium excretion while water is retained due to high ADH level, further decreases serum [Na + ] - Serum [Na + ] >120 meq/l - Identify if the patient is euvolemic or subtle hypovolemic Invest igat ions - Urine [Na + ] - FeNa + (fract ional excret ion) - Norm al saline challange Euvolem ic and subt le hypovolem ic (cont.) Hypervolem ic - Significant edema S 3 gallop, ascites Com m on causes - Heart failure - Hx: MI, HTN, alcohol abuse - PE: JVD, S 3 gallop, crackles, peripheral edema - ECG, echocardiogram - Cirrhosis - Hx: chronic hepatitis, alcohol abuse - PE: scleral icterus, spider angioma, ascites, gynecomastia, splenomegaly - Sretum albumin - ALT, AST, bilirubin, GGT, ALP - PT, PTT - HBsAg, hepatitis C Ab - Liver U/S and Doppler - Renal failure - Serum BUN, creatinine, egfr - Urinalysis - Nephrotic syndrome - Hx: foamy urine, DM, SLE - Serum albumin, BUN, creatinine - Urinalysis - Spot (random) protein-to-creatinine ratio - 24-hr urine for total protein - Preeclampsia (toxemia)

3 Subt le hypovolem ic Assess t he pat ient 's urine [Na + ] - Urine [Na + ] <10 meq/l Indicat es "ext rarenal salt loss" Cau ses - Salt and water loss with free water intake - Dehydration - Vomiting - Diarrhea - Urine [Na + ] >20 meq/l Indicat es "renal salt loss" Cau ses - Diuretics - ACE inhibitors - Nephropathies (Addison disease) - Hypoaldosteronism - High serum [K + ] - Cerebral sodium-wasting syndrome Legals: 2018 Kitchanan Kosalathip. All right reserved. Non-profit educational usage is permitted under principle of fair use. Disclaimer and denial of liability: Although the author has made every effort to ensure that the information in this publication was correct at published time, the author does not assume and hereby disclaim any liability to any party for any loss, damage, or disruption

4 Euvolem ic and subt le hypovolem ic - Serum [Na + ] >120 meq/l - Identify if the patient is euvolemic or subtle hypovolemic Invest igat ions - Urine [Na + ] - FeNa + (fract ional excret ion) - Norm al saline challange Logics behind ident ificat ion of " Subt le hypovolem ia" (1) Urine Na + and FeNa + (fract ional excret ion) - FENa + compares fraction of sodium excreted to fraction of sodium filtered. - FENa + = (UNa + PCr) (PNa + UCr) - Hypovolemia promotes Na + reabsorption, leading to: - Low urine [Na + ] (<30 m Eq/ L) SE 63?80%, SP %, LR+ 2.2-?, LR Low FeNa + (<0.5%) SE 100%, SP 72%, LR+ 3.5, LR- 0 - In contrast, euvolemia does not have a stimulus to reabsorb urine sodium, thus: - Higher urine [Na + ] (>30 m Eq/ L) - Higher FeNa + (>0.5%) (2) Response t o a "sm all saline challenge" - In hypovolemic patients, ADH is suppressed as the plasma volume expands, thus: - Wat er diuresis - Rise in t he serum [Na + ] - In euvolemic patients, ADH is not volume dependent and persists despite the saline challenge, resulting in retention of the water whereas the sodium is excreted. - Paradoxical fall in t he serum [Na + ] - Urine [Na + ] <30 meq/l - FeNa + <0.5% - Normal saline challange shows significant increase in serum [Na + ] Rule out false-post ivie result s (low urine [Na+] and FeNa+ in euvolem ic pat ient s) - Psychogenic polydipsias (due to dilution of the excreted Na + in vast quantities of water) - SIADH patients that ingest little sodium (causing decreased urinary Na + output) Ot herw ise - Subt le hypovolem ic - Urine [Na + ] >30 meq/l - FeNa + >0.5% - Normal saline challange shows no significant change or fall in serum [Na + ] Rule out false-negat ive result s (high urine [Na+] and FeNa+ in hypovolem ic pat ient s) - Diuretics (hypoaldosteronism directly causes urinary sodium wasting) - Vomiting with accompanying metabolic alkalosis (metabolic alkalosis causes an obligatory urinary HCO 3? and Na + loss; urine Cl? may be low and diagnostic) Ot herw ise - Euvolem ic (cont.) Euvolem ic Drugs - Thiazide diuretics* - ADH analogues - Vasopressin - Desmopressin acetate (DDAVP) - Oxytocin (including near-delivery pregnent women) - ACE inhibitors - Chlorpropamide (PREV 6-7%) - Carbamazepine - Antidepressants - Ttricyclics - SSRIs - Antipsychotics - NSAIDs - Ecstasy (MDMA) - Others (eg, cyclophosphamide, vincristine, nicotine, opioids, clofibrate) - Severe hypothyroidism (TSH markedly elevated) - Secondary renal insufficiancy (low serum cortisol, hyperkalemia) - SIADH (syndrome of inappropriate antidiuretic hormone secretion) (urine osmolarity increases) - Cancers (eg, pancreas, lung) - CNS disease (eg, cerebrovascular accident, trauma, infection, hemorrhage, mass) - Pulmonary diseases (eg, infections, respiratory failure) - Exercise-associated hyponatremia (EAH) Special cases Urine osm olarit y <100 m Osm / L - Psychogenic polydipsia - Ecstasy use - Beer potomania Post operat ive - Postopetaive patients receiving nacotics with overaggressive IV fluid treatment

5 Hyponat rem ia m anagem ent Isot onic Ident ify life-t hreat ening pat ient s - Severely sym t om at ic pat ient s (coma, seizures) - Acut e (new onset in the last hr) Hypert onic or isot onic - Do not give extra salt or saline Monit oring - observation - Serum [Na + ] q4?6h until >125 meq/l Non-life t hreat ening pat ient s IMMEDIATE INTERVENTION REQUIRED - Urgent 4?6 meq/l increases in serum [Na + ] - In chronic severe symptomatic hyponatremia, correction rate should not exceed?0.5-1 meq/l/hr - - Hypert onic saline 100 m L 3% NaCl IV over 10 m in (for severe sym pt om s) 100 m L 3% NaCl IV 0.5?2 m L/ kg/ h (for m ild t o m oderat e sym pt om s) - May repeat a second dose if needed Discontinues if (any): - Life-threatening symptoms abate - Serum [Na+]?120 meq/l S/E - Central pontine myelinolysis (brainstem damage) - Serum [Na+]?120 meq/l Hypervolem ic and euvolem ic - Water and fluid restriction - Diurtics (in hypervolemic hyponatremia as appropriate) w at er rest rict ion fails in SIADH - Demeclocycline (which induces nephrogenic diabetes insipidus) Ot her chronic Assess risk of osm ot ic dem yelinat ing syndrom e (ODS) Risk fact ors - Hypovolemic hyponatremia - Diuretic-associated hyponatremia - Treated cortisol deficiency - Serum [Na + ] < 105 meq/l - Hypokalemia - Alcohol abuse - Malnutrition - Advanced liver disease Overcorrect ion (serum [Na + ] increment exceed maximal rate of correction) - Prevent osmotic demyelinating syndrome (ODS) Init iat e reverse t herapy - 2?4 µg desmopressin IV q8h - 3 ml/kg IV D5W over 1 hr - Repeat until serum sodium within limit range - Discontinues vaptans - Follow serum sodium hourly - In high risk group, 4?6 meq/l/d increases in serum [Na+] Maximum?13 meq/l/d Maximum?18 meq/l/2d - In low high group, 4?8 meq/l/d increases in serum [Na+] Maximum?8 meq/l/d - Normal saline IV ± vaptans - Stopped once daily goal is met - Replace urinary water losses (any, by rank of preferences): - D5W IV - Water (by mouth) - DDAVP (may be ineffective in patients treated with vaptans)