Beer Drinker's Potomania AM Report 10/26/09 Darrell Laudate

Hyponatremia Occurs if free water intake is greater than free water output via one or both of the following mechanisms:   1.  Increased free water supply 2.  Impaired free water excretion by kidney Too much ADH Volume depletion Real or Effective (CHF, Liver Disease) Endocrine Thyroid, Adrenal Inappropriate ADH Too few nephrons (Renal failure)

Recall the Effect of Vasopressin/ADH 1) Increases H2O permeability of DCT and CT   allows H20 reabsorption and excretion of a smaller volume of concentrated urine  (aka antidiuresis) 2) Increases the Urea permeability of the papillary portion of the collecting duct increased reabsorption of urea into the medullary interstitium, down the concentration gradient created from the removal of water in the cortical collecting duct. 3) Stimulates sodium reabsorption in the thick-ascending loop of Henle by increasing the activity of the Na+-K+-2Cl--cotransporter.   Overall, these effects increase Urine osm & decreased urine excretion

Hyponatremia *Note: all have ↑ADH Serum OSM Low Normal High ECFv * Low SIADH: inappropriate Rest: appropriate Hyponatremia Serum OSM Low Normal High Marked hyperlipidemia (lipemia, TG >35mM) Hyperproteinemia (Multiple myeloma) Hyperglycemia Mannitol Hypotonic Hyponatremia ECFv * Low High Normal CHF Cirrhosis Nephrosis Hypothyroidism AI SIADH Reset Osmostat Water Intoxication 1° Polydipsia TURP post-op Renal loss (UNa > 20) Diuretics Thiazide K-sparing ACE-I, ARB IV RTA, Hypoaldo Cerebral salt wasting Extra-renal loss (UNa <10) Bleeding Burns GI (N/V, diarrhea) Pancreatitis

Diagnosis of Hyponatremia Plasma osmolality nml 275 to 290 mosmol/kg reduced in most hyponatremic patients, because it is primarily determined by the plasma [Na] and accompanying anion normal osmolality (Iso-osmolar) aka Pseudohyponatremia with hyperlipidemia or hyperproteinemia

Diagnosis of Hyponatremia (cont.) Plasma Osmolarity (cont.) Hyperosmolar Hyponatremia Recall Calculated Osm = 2(Na+K) + BUN/2.8 + Glucose/16 Gap (measured - calculated) > 10 indicates osmotic substance that is not Na, Glucose, or BUN Endogenous substances Acetone, Renal Failure, Lactate Exogenous (Methanol, Ethylene Glycol, Ethanol, Glycine, Mannitol)

Diagnosis of Hyponatremia (cont.) Urine osmolality used to distinguish between impaired water excretion (which is present in almost all cases) and primary polydipsia  normal response to hyponatremia  is to completely suppress ADH secretion results in excretion of a maximally dilute urine with an osm below 100 mosmol/kg and a SpG ≤1.003 Values above this level indicate an inability to normally excrete free water (i.e continued secretion of ADH) Most hyponatremic patients have a relatively marked impairment in urinary dilution that is sufficient to maintain the urine Osm > or = 300 mosmol/kg

Diagnosis of Hyponatremia (cont.) Urine Osm (cont) Urine Osm < 100 in the following conditions Psychogenic Polydipsia Massive H20 intake overwhelms H20 excretion beer drinkers potomania (AKA Tea & Toast diet, malnutrition) dietary solute intake such as Na, K, protein is decreased therefore solute excretion is so low that the rate of H20 excretion is markedly diminished even though urinary dilution is intact (Also Reset osmostat after a H20 load appropriately suppresses ADH release)

Diagnosis of Hyponatremia (cont.) Urine sodium concentration used to distinguish between hyponatremia caused by a decreased effective arterial blood volume and euvolemic hyponatremia.1 usually below 25 meq/L in hypovolemia unless there is renal salt-wasting, due most often to diuretic therapy and infrequently to adrenal insufficiency or cerebral salt-wasting) usually above 40 meq/L in patients with the SIADH who are normovolemic and whose rate of sodium excretion is determined by sodium intake, as it is in normal subjects.2

Diagnosis of Hyponatremia (cont.) Urine Na (cont) In addition to the initial value, serial monitoring of the urine [Na] may be helpful in selected cases in which the correct diagnosis may not be apparent If hypovolemic, isotonic saline should suppress the hypovolemic stimulus to ADH release promoting the excretion of dilute urine and rapid correction of the hyponatremia. If SIADH, ADH release occurs independently of the volume status urine osmolality remains high but urine Na excretion is promoted by volume expansion and often rises above 40 mEq/L. 

Diagnosis of Hyponatremia (cont.) Urine Na (cont) In addition to the initial value, serial monitoring of the urine [Na] may be helpful in selected cases in which the correct diagnosis may not be apparent If hypovolemic, isotonic saline should suppress the hypovolemic stimulus to ADH release promoting the excretion of dilute urine and rapid correction of the hyponatremia. If SIADH, ADH release occurs independently of the volume status urine osmolality remains high but urine Na excretion is promoted by volume expansion and often rises above 40 mEq/L. 

Additional labs FeNa Plasma uric acid initial water retention and volume expansion in the SIADH is frequently associated with hypouricemia (due to increased uric acid excretion in the urine).2 Plasma urea Hypervolemia also increases urea clearance such that hyponatremia of SIADH usually is associated with a BUN of < 5 mg/dL (1.8 mmol/L).3 caution in older patients as BUN is seldom this low secondary to decreased FeBUN that occurs with aging.4 i.e the absence of a low BUN cannot be used to exclude SIADH in older patients

Additional Labs Acid-base and potassium balance, E.g: Metabolic alkalosis and hypokalemia Diuretic use or vomiting Metabolic acidosis and hypokalemia Diarrhea or laxative abuse, Metabolic acidosis and hyperkalemia Adrenal insufficiency

Treatment When considering the treatment of patients with hyponatremia, five issues must be addressed: Risk of osmotic demyelination Appropriate rate of correction to minimize this risk Optimal method of raising the plasma sodium concentration Estimation of the sodium deficit if sodium is to be given Management of the patient in whom overly rapid correction has occurred

General principles of treatment Clinical approach to the patient should be primarily determined by the severity of symptoms and the cause of the hyponatremia Symptomatic hyponatremia (seizures, AMS, or coma) likely to occur with an acute (within 24 to 48 hours) and marked reduction in the plasma sodium concentration As opposed to chronic but significant hyponatremia where less severe neurologic symptoms occur fatigue, nausea, dizziness, gait disturbances, forgetfulness, confusion, lethargy, and muscle cramps These symptoms typically do not mandate aggressive therapy

General principles of treatment (cont.) Asymptomatic Hyponatremia Serum [Na] can be raised in these patients by restricting water intake, by giving salt, or by giving vasopressin receptor antagonists   Therapy can also be directed at reversing the underlying disease true volume depletion -  isotonic saline, thus suppressing ADH release adrenal insufficiency - Glucocorticoids to directly suppress  ADH release thyroid hormone replacement in hypothyroidism cessation of a drug that causes SIADH

Rate of correction Plasma sodium concentration should probably be raised by less than 10 meq/L in the first 24 hours and less than 18 meq/L in the first 48 hours.5   This rate of correction is true for any significant hyponatremia being corrected by any method, not simply with hypertonic saline.

Methods of Sodium Correction Water restriction Water restriction to below the level of output is the primary therapy for hyponatremia in edematous states (such as heart failure and cirrhosis), the SIADH, primary polydipsia, and advanced renal failure

Methods of Sodium Correction (cont.) Sodium chloride administration usually as isotonic saline or increased dietary salt given to patients with true volume depletion, adrenal insufficiency, and in some cases of SIADH. contraindicated in edematous patients (eg, heart failure, cirrhosis, renal failure) since it will lead to exacerbation of the edema   Hypertonic saline is generally recommended only for patients with symptomatic or severe hyponatremia.

So how much (fluids) do I give? The degree to which one liter of a given solution will initially raise the plasma sodium concentration (PNa) can be estimated from the following formula: Increase in PNa = (Infusate [Na] - PNa) ÷ (TBW + 1) Recall TBW = lean body weight x 0.5 for women TBW = lean body weight x 0.6 for men This equation should only serve as a initial guide, ultimately close, frequent Na monitoring should dictate your infusion

Recall Infusate Characteristics IV Fluids One liter of LRS contains: 130 mEq of sodium ion (130 mmol/L), 109 mEq of chloride ion (109 mmol/L). 28 mEq of lactate (28 mmol/L), 4 mEq of potassium (4 mmol/L), 3 mEq of calcium ion (1.5 mmol/L) One liter of NS contains: 154 mEq/L of Na+ and Cl− One liter of 3% saline contains: 514 mEq/L of Na+ and Cl−

Treatment (cont.) Vasopressin Receptor antagonists (tolvaptan and conivaptan) can be considered for use in: SIADH Heart failure Conivaptan may also have a favorable effect on hemodynamics via V1a blockade, further studies warranted Cirrhosis tolvaptan concerns that the concurrent V1a receptor blockade might lower the blood pressure and increase the risk of variceal bleeding, recall vasopressin is used to treat active bleeding  Careful monitoring is required as overly rapid correction can occur with these agents high cost is often an issue as well

References Rose et al. Clinical Physiology of Acid-Base and Electrolyte Disorders. 5th ed, McGraw-Hill, NY, 2001, pp. 720-723. Graber et al. The electrolytes in hyponatremia.  Am J Kidney Dis 1991 Nov;18(5):527-45 Decaux et al. Uric acid, anion gap and urea concentration in the diagnostic approach to hyponatremia. Clin Nephrol 1994 Aug;42(2):102-8 Musch et al. Age-related increase in plasma urea level and decrease in fractional urea excretion: clinical application in the syndrome of inappropriate secretion of antidiuretic hormone.  Clin J Am Soc Nephrol. 2006 Sep;1(5):909-14. Epub 2006 Jul 6 Verbalis et al.  Hyponatremia treatment guidelines 2007: expert panel recommendations. J Med. 2007 Nov;120(11 Suppl 1):S1-21.