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hyponatremia

Classification: - hypertonic - serum osmolality > 295 mOsm/kg H2O - isotonic - serum osmolality 275-295 mOsm/kg H2O - hypotonic - serum osmolality < 275 mOsm/kg H2O - hypervolemic, isovolemic, or hypovolemic Etiology: === edema-forming states (hypotonic, hypervolemic) === 1) mechanism a) decreased effective arterial blood volume b) sodium & water retention by the kidney - water retention exceeds sodium retention in pregnancy [4] c) excessive total body sodium d) excessive extravascular fluid (3rd spacing) 2) congestive heart failure (CHF) 3) nephrotic syndrome 4) hepatic cirrhosis 5) acute or chronic renal failure === volume depletion (hypotonic. hypovolemic) === 1) mechanism a) renal salt loss b) extrarenal salt loss c) replacement with hypotonic fluid d) stimulation of ADH despite hypotonicity (hypovolemia overrides hyponatremia) 2) urine Na+ < 10 meq/L a) gastrointestinal loss from vomiting or diarrhea b) 3rd space loss 1] peritonitis 2] pancreatitis c) skin losses d) lung & respiratory tract losses 3) urine Na+ > 20 meq/L a) pharmacologic agents 1] diuretics: thiazide diuretics more commonly than loop diuretics [31]* 2] mannitol 3] enemas b) hypoaldosteronism 1] Addison's disease 2] hyporenin hypoaldosteronism c) salt-losing nephritis d) osmotic diuresis e) renal tubular acidosis (RTA) f) obstruction * in the elderly mainly associated with diabetes mellitus & diuretics [18] === normal extracellular volume (hypotonic, normovolemic) === 1) syndrome of inappropriate antidiuretic hormone secretion (see SIADH) a) malignancy (carcinoma causing ectopic production of ADH) b) CNS disease c) pulmonary disorders d) pharmacologic agents e) postoperative after orthopedic surgery [26], hypophysectomy [33,35,36] 2) pharmacologic agents that potentiate renal effect of ADH a) chlorpropamide b) carbamazepine c) NSAIDs d) cyclophosphamide 3) pharmacologic agents that produce ADH-like effect a) oxytoxin b) desmopressin 4) administration of hypotonic fluids (urine Na+ < 10 meq/L) a) postoperative b) psychogenic polydipsia 5) low salt intake (anorexia) [4,11] 6) severe hypothyroidism 7) cortisol deficiency or panhypopituitarism 8) pregnancy (mild hyponatremia due to changes in ADH response to osmolality) [4] 9) most common 60% [31] === hyponatremia with hypertonicity or hyperosmolarity (hypertonic) === 1) mechanism: - osmotically active substance causes movement of intracellular fluid extracellularly 2) hyperglycemia (a decrease of 1.6 meq/L for each 100 mg/dL increase in plasma glucose) [29]* 3) increased serum urea, alcohols, mannitol, sorbitol, glycine * in the elderly mainly associated with diabetes mellitus & diuretics [18] === pseudohyponatremia (isotonic hyponatremia)* === 1) isotonic hponatremia occurs because of non-aqueous volume occupied by lipid in hypertriglyceridemia & perhaps protein in monoclonal & polyclonal gammopathies 2) ion-specific electrodes used in most modern instruments measures may be falsely low when plasma contains < 93% H2O [4] - flame photometry may be more reliable measure of sodium 3) see Laboratory (below) for expected serum sodium in the presence of hyperglycemia * distinguish from true hyponatremia caused by hyperosmolarity by measuring serum osmolality [4] Epidemiology: - most common electrolyte abnormality in hospitalized patients - more common in elderly patients [17] Clinical manifestations: 1) symptoms related to etiology of hyponatremia - orthostasis associated with volume depletion, but not edema-forming states 2) symptoms related to degree of hyponatremia & acute vs chronic nature of the disorder a) symptoms do not appear until: 1] serum sodium drops below 125 meq/L suddenly 2] much lower if hyponatremia is chronic b) overt neurologic symptoms are most often due to serum sodium levels < 115 mEq/L [17] 3) neurologic manifestations predominate a) headache b) lethargy, apathy, muscle weakness, muscle cramps c) agitation/irritability d) nausea/vomiting e) dysgeusia [6] f) cognitive impairment 1] disorientation 2] confusion g) decreased level of consciousness h) decreased deep tendon reflexes i) muscle twitching j) grand mal seizures k) Cheyne-Stokes respirations l) coma & death may occur with [Na+] < 110 meq/L Laboratory: 1) serum osmolality & urine osmolality a) serum osmolality is decreased except in hyperosmolar conditions, i.e. diabetes & pseudohyponatremia (isotonic hyponatremia) b) urine osmolality - < 100 mOsm kg H2O suggests appropriately suppressed ADH - primary polydipsia - decreased solute intake (anorexia) [4,11] - > 100 mOsm kg H2O suggests ADH excess (SIADH) - elderly may not be able to dilute urine < 150 mOsm/kg H2O, thus > 150 mOsm kg H2O may suggest ADH excess (SIADH) in the elderly [26] - also consistent with volume depletion - adrenal insufficiency & hypothyroidism may present similarly to SIADH (see below) 2) serum chemistries a) electrolytes 1] serum sodium - mild hyponatremia, serum Na+ < 136 meq/L - severe hyponatremia, serum Na+ < 125 meq/L 2] serum K+: a] hypokalemia if volume depletion with fluid loss secondary to renal or GI etiology b] normal in SIADH 3] serum bicarbonate: normal in SIADH 4] serum chloride: normal in SIADH b) serum glucose - a decrease in serum Na+ of 1.6 meq/L for each 100 mg/dL increase in serum glucose [4] c) serum urea nitrogen: - BUN/creatinine ratio > 20 with volume depletion d) serum creatinine e) serum uric acid 3) urine chemistries a) urine sodium 1] urine sodium < 20 meq/L in: a] edema-forming states - cirrhosis - CHF - nephrotic syndrome b] hypovolemia of extrarenal origin c] decreased solute intake (anorexia) [4,11,35] 2] urine sodium > 20 meq/L in: a] renal failure b] hypovolemia of renal origin c] SIADH b) urine creatinine 4) fractional excretion of sodium (FENA) 5) thyroid function tests if indicated 6) adrenal function tests if indicated - adrenal insufficiency - serum cortisol 8 AM, plasma ACTH - hyperkalemia, acidosis, history of autoimmune disease, weight loss - first diagnostic tests after serum sodium & serum K+ in a patient with history of opioid abuse & symptoms of secondary adrenal insufficiency [4] 7) see ARUP consult [8] Special laboratory: - geriatric assessment tools* demonstrate worse function it elderly patients with hyponatremia & improvement with improvement of serum sodium [38] * the geriatric assessment tools used included - Hindi mental status examination - Barthel's index of activities of daily living, * timed get-up-&-go test * dynamometer hand grip strength Complications: - increased risk of myocardial infarction & death (mild hyponatremia, serum Na+ < 136 meq/L) [7] - increased risk of perioperative mortality (even mild hyponatremia, serum Na+ < 135 meq/L) [9] - seizures, coma - high mortality associated with severe hyponatremia (< 125 meq/L) [17] - mortality > 50% if serum sodium is < 105 meq/L - mortality is higher among alcoholics [17] - rapid overcorrection of hyponatremia is common; - osmotic demyelination (central pontine myelinolysis) is rare [32] Management: 1) establish urgency of treatment a) brain edema, uncontrolled seizures & herniation are b) acute onset of hyponatremia, seizures, & stupor/coma indicate urgent treatment 2) urgent treatment for symptomatic patients a) normal saline to restore euvolemia in hypovolemic patients (NEJM) [36] - infusion of normal saline can result in worsening of hyponatremia [2] b) IV furosemide (Lasix) may be given for volume overload c) 3% saline* - 100 mL bolus for acute symptomatic isovolemic hypotonic hyponatremia [4] (polydipsia or administration of hypotonic fluids) - increase serum sodium 1.0-2.0 meq/L/hour; 0.5 meq/L/hour [31] - total increase of 4-6 meq/L/24 hours to max of 8 meq/L/24 hours [4] - 6-10 meq/L/24 hours aligns with guidelines (2023) [39] - maintain this serum sodium for 24 hours [4] - central pontine myelinolysis is a rare complication of too rapidly correcting serum sodium - desmopressin with 3% saline for safer increase in serum sodium [4] - D5W +/- desmopressin for overcorrection of hyponatremia [2,23]; - ref [4] recommends D5W + desmopressin - 3% saline bolus 2 mL/kg every 6 hours during 1st 24 hours safe [28,30] d) serum Na+ is usually corrected to 120 meq/L e) conivaptan or tolvaptan IV for life-threatening euvolemic & hypervolemic hyponatremia in hospitalized patients [4,5] 3) asymptomatic patients a) water restriction unless patient is volume contracted - 500 to 1000 mL/day (restriction of all fluids) [33] - indicated for patients with cirrhosis when serum Na+ < 120 meq/L [4,10] b) normal saline for hypovolemia c) hypervolemia - chronic heart failure, cirrhosis, chronic renal failure - fluid restriction - loop diuretic - tolvaptan 15-60 mg PO QD d) SIADH - free water restriction alone is not sufficient - demeclocycline - do NOT use in patients with cirrhosis - tolvaptan 15-60 mg PO QD [20] - increase solute intake (urea 15 g BID mixed with fruit juice) for low plasma osmolality & high urine osmolality not responding to fluid restriction [33,34] 4) address underlying disease processes 5) unless hyponatremia is indicated as acute, treat a chronic hyponatremia [2] * 3% saline also indicated for serum Na+ < 130 meq/L immediately preceding liver transplantation [4]

Related

drugs associated with hyponatremia fractional excretion of sodium (FENA) sodium (Na+) in serum

Useful

hypernatremia

General

electrolyte disorder sign/symptom

References

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