Basic approach to: Hyponatremia Adley Wong, MHS PA-C

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2016 Topics in Acute and Ambulatory Care CAPA Conference 2018 for Advanced Practice Providers Basic approach to: Hyponatremia Adley Wong, MHS PA-C Goals Physiology of hyponatremia Why we care about hyponatremia Algorithm for evaluating hyponatremia Differentiating hypovolemic vs euvolemic hyponatremia Management of hyponatremia Objective: Hyponatremia is a water problem Hyponatremia is a water problem Excess water compared to sodium- regardless of volume status.

Normal response to hyponatremia Ability to excrete water is so great that water retention resulting in hyponatremia usually doesn t happen When your body senses that you have too much water this happens: Question When you drink 2 glasses of water, what happens to your serum osmolality? A. Increases B. Decreases Osmolality Osmolality= total concentration of solutes stuff in water. Normal Serum osm: 285-310 -Before water intake -Serum osm: 285-310 -After 2 cups of water intake -Serum osm: 275

Question After you drink 2 cups of water, your serum osmolality decreases. What happens to your anti-diuretic hormone (ADH) levels? A. Increase B. Decrease ADH= ANTI-diuretic hormone, helps retain water Decreases! Lack of ADH allows you to excrete free water. High serum osmolality Low serum osmolality There are 2 triggers for ADH Osmolality (amount of solute in water). When the plasma osmolality is low (more water than solute), ADH is off When the plasma osmolality is high (more solute than water), ADH is on. Volume Extreme Hypovolemia/Decrease in effective blood volume. During times of hypovolemia (ie. Shock), ADH kicks in

Objective: Physiology of Hyponatremia Remember hyponatremia is a WATER PROBLEM. One becomes hyponatremic when there is a problem with EXCRETION of free water Virtually all hyponatremic patients (exception of those with renal failure and primary polydipsia) have an excess of ADH. We care about hypoosmolar hyponatremia Cerebral edema! Symptoms of hyponatremia Serum sodium levels: Under 135 meq/l = Hyponatremia Below 125 meq/l --- Nausea and malaise Between 115 and 120 meq/l --- headache, lethargy and obtundatation.. Less than 115mEq/L-- More severe changes of seizures and coma Depends on chronicity: Chronic= few symptoms. Acute=more symptoms (esp acute <24hrs).

Objective: Algorithm for hyponatremia 1) Check serum osmolality. True hyponatremia is hypoosmolar Pseudohyponatremia Low plasma [Na+] with normal plasma osmolality Severe hyperlipidemia or hyperproteinemia Low plasma [Na+] with elevated plasma osmolality Hyperglycemia- Dilution, glucose causes water movement out of the cells and a reduction in the plasma Na+. Plasma Na+ concentration fall 1 meq/l for every 62mg/dL rise in serum glucose (above 100mg/dL). Algorithm 1) Check serum osmolality. True hyponatremia is hypoosmolar (RELATIVE more water than solute) 2) Check volume status, urine sodium and urine osm Hypovolemic Hyponatremia Euvolemic Hyponatremia Hypervolemic Hyponatremia

Volume status can be challenging Evaluate: Vital signs Orthostatic vital signs Jugular venous pressure, skin turgor, mucous membranes, peripheral edema Blood urea nitrogen Uric acid Objective: Differentiating between hypovolemia and euvolemia Hypovolemic Euvolemic Signs/Symptoms: Dry mucous membranes, vomiting, diarrhea, tachycardia, orthostatic. Labs: Elevated BUN/Cr ratio >20:1, Urinary sodium<20 meq/l, FENA<1% or FEUREA<35%, elevated uric acid Signs/Symptoms: Absence of hypovolemia Labs: Normal BUN/Cr ratio. Urine sodium>20 meq/l ****Urine sodium may not always correlate with volume status (i.e. diuretic use can elevate urine sodium; low-salt diet can artificially lower urine sodium) Hypovolemic hyponatremia Fluid losses from GI tract, kidneys or skin RX: Isotonic saline

Euvolemic Hyponatremia Volume status is normal Low osmolality (true hyponatremia) = expect ADH to be OFF = expect dilute urine (low urine osm, <100 mosm per kg) Euvolemic hyponatremia Urine osm >100 mosm per kg Syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypothyroidism, adrenal insufficiency, drug use Urine osm <100 mosm per kg Primary polydipsia, low solute intake (beer potomania syndrome) Variable urinary osm Reset osmostat RX: Fluid (Free water) restriction. Treat underlying condition. Hypervolemic hyponatremia Volume overloaded states (Systolic Heart failure, cirrhosis, hypoalbuminemia) Intravascular volume depletion = increased ADH Urine sodium <20 meq/l RX: Fluid & sodium restriction, diuresis Renal failure- kidneys can t excrete free water efficiently (not ADH) Urine sodium >20 meq/l RX: Fluid & sodium restriction, dialysis

RECAP: Check serum osm Check volume status// urine osm and urine sodium Hypovolemic hyponatremia RX: Isotonic saline Euvolemic hyponatremia RX: Fluid (free water) restriction, treat underlying condition Hypervolemic hyponatremia RX: Fluid (free water) and sodium restriction, Diuresis, treat underlying condition Case Applying the hyponatremia algorithm to determine the ETIOLOGY of hyponatremia Ms. D is a 85 y/o F Zumba instructor with PMH breast cancer who presents for an evaluation of hyponatremia. Case HPI: Hyponatremia 128 in June and 127 in July. Baseline serum sodium 135-137 meq/l from 2010-2015. No new meds Drinks 4-5 ten ounce water bottles daily. No changes in weight. Good appetite. SBP in low 100s which is baseline for her. Complains of fatigue over the past few months but still exercising with Zumba daily.

Case VS: Afebrile, BP 90/50 (SBP low 100s normal for her), not orthostatic, HR 70, RR 18, Room Air Pertinent positives: Gen: Thin NAD HEENT: Moist mucous membranes Neck: No JVD CVS: RRR, no m/r/g Lungs: CTAB GI: Soft, NT/ND Extremities: No edema Skin: Normal skin turgor Labs: Serum osm- 270, Urine osm of 192, Urine sodium 24 Na- 127/ K- 5.4 /Bicarb- 29/ BUN- 14/Cr- 0.64/ Glucose 110/ TSH normal; cortisol normal Case: What is the differential? Primary polydipsia Renal failure Hypothyroidism Adrenal insufficiency SIADH Medication induced Case: Applying the algorithm 1) Serum osm- 270, true hyponatremia 2) Volume status: Euvolemic BP is 90/50 but normal for her. She is not orthostatic. Not tachycardic. JVP is not elevated. Normal skin turgor and moist mucous membranes. No peripheral edema. BUN<20:1. Unremarkable uric acid levels.

Case: Working up euvolemic hyponatremia Check urine sodium and urine osm to help clarify differential after volume status Urine sodium is 24 (expect >20 in euvolemia) Urine osm of 192 (expect <100, seems inappropriately high) If euvolemic & Urine osm >100 mosm per kg DDx: SIADH, hypothyroidism, adrenal insufficiency, drug use Case: What is the highest on your differential? Primary polydipsia (based on algorithm and history, expect urine osm <100) Renal failure (normal Cr) Hypothyroidism (normal TSH of 1.49) Adrenal insufficiency (normal AM cortisol) SIADH Medication induced (reviewed medications) SIADH Characterized by nonphysiologic release of ADH (ie. Not due to usual stimuli such as hyperosmolality or hypovolemia)

Etiology SIADH can be produced by enhanced hypothalamic secretion, ectopic (nonhypothalamic) hormone production, the potentiation of ADH effect or the administration of exogenous ADH. Causes of SIADH Increased hypothalamic production of ADH Neuropsychiatric disorders/cns Infections meningitis, encephalitis, abscess, herpes zoster Vascular: thrombosis, subarachnoid or subdural hemorrhage, Neoplasma: primary or secondary Psychosis Pulmonary disease may be from decrease pulmonary venous return leading to volume receptors Pneumonia: viral, bacteria, or fungal TB Acute respiratory failure Other: Asthma, atelectasis, pneumothorax Postoperative patient inappropriate ADH secretion is common and persists for 2 5 days. Appears to be mediated by pain afferents Severe nausea Drugs: SSRIs, thiazides Causes of SIADH Ectopic (nonhypothalamic production of ADH) Carcinoma: small cell of lung, bronchogenic, duodenum, pancreas, thymus, olfactory, neuroblastoma Potentiation of ADH effect IV cyclophosphamide

Diagnosis of SIADH Summary Hyponatremic. Hypoosmolar (Serum osm low) Euvolemic. Ruled out for other causes of Euvolemic Hyponatremia. Urine osm inappropriately high (>100 mosmol/kg) Urine sodium normal (usually greater than 20 meq/l) Hypouricemia Treatment for this patient For our patient with SIADH, what would be the appropriate management? A. Give normal saline B. Fluid (free water) restriction to 0.8L C. Give salt tablets Treatment for this patient For our patient with SIADH, what would be the appropriate management? A. Give normal saline- NO. She will keep more water and serum sodium will fall B. Fluid (free water) restriction to 0.8L daily- YES C. Give salt tablets- MAYBE

Major treatment Hypovolemic Hyponatremia Isotonic Saline Euvolemic Hyponatremia Fluid (free water) restriction, treat underlying condition Hypervolemic Hyponatremia Fluid (free water) and sodium restriction, Diuresis, treat underlying condition For AKI, fluid/sodium restriction and possible dialysis Treatment: Rate of Correction Why worry? Overly rapid correction can lead to cerebral dehydration and cause osmotic demyelination Paraparesis, dysarthria, dysphagia, coma, seizures Those at greatest risk are individuals with chronic hyponatremia (brain cells have adapted to hyponatremia) Treatment: Goals Chronic Hyponatremia/asymptomatic: Rate of correction: <10-12 meq/l in first 24hrs (<0.5 meq/l per hour) and <18 meq/l in 48hrs. Acute Hyponatremia/symptomatic: Risk of untreated hyponatremia and cerebral edema is greater than the potential harm of overly rapid correction Hypertonic 3% saline infused at a rate of 0.5 to 2 ml/kg/hour until symptoms resolve Increase of 4-6 meq/l usually sufficient to reduce symptoms Should NOT exceed 10-12mE/L in first 24hrs (same as above) Loop diuretics may be used if concurrent volume overload

Thank you! Special Thanks to: Dr. Pedram Fatehi, Dr. Tara Chang and Shira Simpson PA-C! Questions? AdleyWong@stanfordhealthcare.org Sources Rose, Burton David. (2001). Clinical Physiology of Acid-Base and Electrolyte Disorders. New York: McGraw-Hill. Gilbert, Scott J., et al. (2014). National Kidney Foundation s Primer on Kidney Diseases. Philadelphia: Elsevier. Braun, M.M., Barstow, C.H., Pyzocha, N.J. (2015). Diagnosis and Management of Sodium Disorders: Hyponatremia and Hypernatremia. Am Fam Physician. 2015; 91 (5): 299-307. Retrieved from: http://www.aafp.org/afp/2015/0301/p299.html Treatment of hyponatremia: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and reset osmostat. UptoDate, 10, June 2018.