The human body at birth is approximately 75% water by weight. By 1 month this value decreases to 65%, and by adulthood to 60% for males and 50% for females. The higher fat content in females decreases water content. For the same reason, obesity and advanced age further decrease water content.
The normal adult daily water intake averages 2500 mL, which includes approximately 300 mL as a byproduct of the metabolism of energy substrates. Daily water loss averages 2500 mL and is typically accounted for by 1500 mL in urine, 400 mL in respiratory tract evaporation, 400 mL in skin evaporation, 100 mL in sweat, and 100 mL in feces. Evaporative loss is very important in thermoregulation because this mechanism normally accounts for 20% to 25% of heat loss.
Both ICF and ECF osmolalities are tightly regulated to maintain normal water content in tissues. Changes in water content and cell volume may induce significant impairment of function, particularly in the brain (see later discussion).
RELATIONSHIP OF PLASMA SODIUM CONCENTRATION, EXTRACELLULAR OSMOLALITY, & INTRACELLULAR OSMOLALITY
The osmolality of ECF is equal to the sum of the concentrations of all dissolved solutes. Because Na+ and its anions account for nearly 90% of these solutes, the following approximation is valid:
Moreover, because ICF and ECF are in osmotic equilibrium, plasma sodium concentration [Na+]plasma generally reflects total body osmolality:
Because sodium and potassium are the major intra- and extracellular solutes, respectively:
Combining the two approximations:
Using these principles, the effect of isotonic, hypotonic, and hypertonic fluid loads on compartmental water content and plasma osmolality can be calculated (Table 49–3). The potential importance of intracellular potassium concentration is readily apparent from this equation. Thus, significant potassium losses may contribute to hyponatremia.
TABLE 49–3Effect of different fluid loads on extracellular and intracellular water contents.1 ||Download (.pdf) TABLE 49–3 Effect of different fluid loads on extracellular and intracellular water contents.1
Total body solute = 280 mOsm/kg × 42 kg = 11,760 mOsm
Intracellular solute = 280 mOsm/kg × 25 kg = 7000 mOsm
Extracellular solute = 280 mOsm/kg × 17 kg = 4760 mOsm
Extracellular sodium concentration = 280 ÷ 2 = 140 mEq/L
Net water gain
B. Isotonic load: 2 L of Isotonic saline (NaCl)
Total body solute = 280 mOsm/kg × 44 kg = 12,320 mOsm
Intracellular solute = 280 mOsm/kg × 25 kg = 7000 mOsm
Extracellular solute = 280 mOsm/kg × 19 kg = 5320 mOsm
Net water gain
|Net effect: Fluid remains in extracellular compartment. |
C. Free water (hypotonic) load: 2 L water
New body water = 42 + 2 = 44 kg
New body osmolality = 11,760 mOsm ÷ 44 kg = 267 mOsm/kg
New intracellular volume = 7000 mOsm ÷ 267 mOsm/kg = 26.2 kg
New extracellular sodium concentration = 267 ÷ 2 = 133 mEq/L
Net water gain
|Net effect: Fluid distributes between both compartments. |
D. Hypertonic load: 600 mEq NaCl (no water)
Total body solute = 11,760 + 600 = 12,360 mOsm/kg
New body osmolality = 12,360 mOsm/kg ÷ 42 kg = 294 mOsm
New extracellular solute = 600 + 4760 = 5360 mOsm
New extracellular volume = 5360 mOsm ÷ 294 mOsm/kg = 18.2 kg
New intracellular volume = 42 – 18.2 = 23.8 kg
New extracellular sodium concentration = 294 ÷ 2 = 147 mEq/L
Net water gain
|Net effect: An intracellular to extracellular movement of water. |
In pathological states, glucose and—to a much lesser extent—urea can contribute significantly to extracellular osmolality. A more accurate approximation of plasma osmolality is therefore given by the following equation:
where [Na+] is expressed as mEq/L and blood urea nitrogen (BUN) and glucose as mg/dL. Urea is an ineffective osmole because it readily permeates cell membranes and is therefore frequently omitted from this calculation:
Plasma osmolality normally varies between 280 and 290 mOsm/L. Plasma sodium concentration decreases approximately 1 mEq/L for every 62 mg/dL increase in glucose concentration. A discrepancy between the measured and calculated osmolality is referred to as an osmolal gap. Significant osmolal gaps indicate a high concentration of an abnormal osmotically active molecule in plasma such as ethanol, mannitol, methanol, ethylene glycol, or isopropyl alcohol. Osmolal gaps may also be seen in patients with chronic kidney failure (attributed to retention of small solutes), patients with ketoacidosis (as a result of a high concentration of ketone bodies), and those receiving large amounts of glycine (as during transurethral resection of the prostate). Lastly, osmolal gaps may also be present in patients with marked hyperlipidemia or hyperproteinemia. In such instances, the protein or lipid part of plasma contributes significantly to plasma volume; although plasma [Na+] is decreased, [Na+] in the water phase of plasma (true plasma osmolality) remains normal. The water phase of plasma is normally only 93% of its volume; the remaining 7% consists of plasma lipids and proteins.
CONTROL OF PLASMA OSMOLALITY
Plasma osmolality is closely regulated by the hypothalamus, which controls both the secretion of antidiuretic hormone (ADH) and the thirst mechanism. Plasma osmolality is therefore maintained within relatively narrow limits by control of both water intake and water excretion.
Secretion of Antidiuretic Hormone
Specialized neurons in the supraoptic and paraventricular nuclei of the hypothalamus are sensitive to changes in extracellular osmolality. When ECF osmolality increases, these cells shrink and release ADH from the posterior pituitary. ADH markedly increases water reabsorption in renal collecting tubules (see Chapter 30), which tends to reduce plasma osmolality back to normal. Conversely, a decrease in extracellular osmolality causes osmoreceptors to swell and suppresses the release of ADH. Decreased ADH secretion allows a water diuresis, which tends to increase osmolality to normal. Peak diuresis occurs once circulating ADH is metabolized (90–120 min). With complete suppression of ADH secretion, the kidneys can excrete up to 10 to 20 L of water per day.
Nonosmotic Release of Antidiuretic Hormone
Carotid baroreceptors (volume receptors), as well as low-pressure volume receptors in the atria, vena cavae, and pulmonary arteries, also influence ADH release. A fall in wall tension results in a reflex increase of ADH secretion from the posterior pituitary. Increased stretch of these receptors not only suppresses ADH secretion, but the increased atrial volume receptor stretch also increases secretion of atrial natriuretic peptide (ANP; see later discussion), which promotes renal excretion of sodium and water. Increased sympathetic activity associated with conditions such as pain, emotional stress, and hypoxia also promotes ADH release.
Activation of osmoreceptors in the lateral preoptic area of the hypothalamus neurons by increases in ECF osmolality induces thirst, stimulating the individual to drink water. Conversely, hypoosmolality suppresses thirst. Thirst is the major defense mechanism against hyperosmolality and hypernatremia, because it is the only mechanism that increases water intake.
HYPEROSMOLALITY & HYPERNATREMIA
Hyperosmolality occurs whenever total body solute content increases relative to TBW and is usually, but not always, associated with hypernatremia ([Na+] > 145 mEq/L). Hyperosmolality without hypernatremia may be seen during marked hyperglycemia or following the accumulation of abnormal osmotically active substances in plasma (see earlier discussion). In the latter two instances, plasma sodium concentration may actually decrease as water is drawn from the intracellular to the extracellular compartment. For every 100 mg/dL increase in plasma glucose concentration, plasma sodium decreases approximately 1.6 mEq/L.
Hypernatremic patients may be hypovolemic, euvolemic, or hypervolemic (Table 49–4). However, hypernatremia is nearly always the result of either a relative loss of water in excess of sodium (hypotonic fluid loss) or the retention of large quantities of sodium. Even when kidney concentrating ability is impaired, thirst is normally highly effective in preventing hypernatremia. Hypernatremia is therefore most commonly seen in debilitated patients who are unable to drink, the very aged, the very young, and patients with altered consciousness. Much of the total body sodium is stored in the skin, bone, and cartilage, which serves as a reservoir for the rest of the body, and patients with dysnatremias may have a low, normal, or high total body sodium content (Figure 49-3).
TABLE 49–4Differential diagnosis of hypernatremia.1 ||Download (.pdf) TABLE 49–4 Differential diagnosis of hypernatremia.1
Body fluid loss (eg, burns, sweating)
Gastrointestinal loss (eg, vomiting, diarrhea, fistulas)
Osmotic diuresis (eg, hyperosmolar nonketotic coma, enteral feeding)
Central diabetes insipidus
Nephrogenic diabetes insipidus
Medications (eg, amphotericin aminoglycosides, lithium, phenytoin)
Sickle cell disease
Suprasellar and infrasellar tumors
Iatrogenic (eg, salt tablet or salt water ingestion, saline infusions, saline enemas, intravenous bicarbonate, enteral feedings)
Solute and water balance and the plasma sodium concentration. Plasma sodium concentration is determined according to the ratio of sodium and potassium to total body water. This concentration is altered by net external intake/output balances of sodium, potassium, and water and by internal exchanges between sodium that is free in solution and sodium that is bound to polyanionic proteoglycans in bone, cartilage, and skin. (Reproduced with permission from Sterns RH. Disorders of plasma sodium—Causes, consequences, and correction. N Engl J Med. 2015 Jan 1;372(1):55-65.)
Hypernatremia & Low Total Body Sodium Content
These patients have lost both sodium and water, but the water loss is in relative excess to that of the sodium loss. Hypotonic losses can be renal (osmotic diuresis) or extrarenal (diarrhea or sweat). In either case, patients usually manifest signs of hypovolemia (see Chapter 51). Urinary sodium concentration is generally greater than 20 mEq/L with renal losses and less than 10 mEq/L with extrarenal losses.
Hypernatremia & Normal Total Body Sodium Content
This group of patients generally manifests signs of water loss without overt hypovolemia unless the water loss is massive. Total body sodium content is generally normal. Nearly pure water losses can occur via the skin, respiratory tract, or kidneys. Occasionally transient hypernatremia is observed with movement of water into cells following exercise, seizures, or rhabdomyolysis. The most common cause of hypernatremia in conscious patients with normal total body sodium content is diabetes insipidus. Diabetes insipidus (DI) is characterized by marked impairment in renal concentrating ability that is due either to decreased ADH secretion (central DI) or failure of the renal tubules to respond normally to circulating ADH (nephrogenic DI). Rarely, essential hypernatremia may be encountered in patients with central nervous system disorders. These patients appear to have “reset” osmoreceptors that function at a higher baseline osmolality.
A. Central Diabetes Insipidus
Lesions in or around the hypothalamus and the pituitary stalk frequently produce DI. DI often develops with brain death. Transient DI is also commonly seen following neurosurgical procedures and head trauma. The diagnosis is suggested by a history of polydipsia, polyuria (often >6 L/d), and the absence of hyperglycemia. In the perioperative setting, the diagnosis of DI is suggested by marked polyuria without glycosuria and a urinary osmolality lower than plasma osmolality. The absence of thirst in unconscious individuals leads to marked water losses and can rapidly produce hypovolemia. The diagnosis of central DI is confirmed by an increase in urinary osmolality following the administration of exogenous ADH. Aqueous vasopressin (5–10 units subcutaneously or intramuscularly every 4–6 h) is the treatment of choice for acute central DI. Vasopressin in oil (0.3 mL intramuscularly every day) is longer lasting but is more likely to cause water intoxication. Desmopressin (DDAVP), a synthetic analogue of ADH with a 12- to 24-h duration of action, is available as an intranasal preparation (10–40 mcg/d either as a single daily dose or divided into two doses) that can be used in both ambulatory and perioperative settings.
B. Nephrogenic Diabetes Insipidus
Nephrogenic DI can be congenital but is more commonly secondary to other disorders, including chronic kidney disease, hypokalemia, hypercalcemia, sickle cell disease, and hyperproteinemias. Nephrogenic DI can also be secondary to the side effects of some drugs (amphotericin B, lithium, demeclocycline, ifosfamide, mannitol). ADH secretion in nephrogenic DI is normal, but the kidneys fail to respond to ADH and urinary concentrating ability is therefore impaired. The diagnosis is confirmed by failure of the kidneys to produce hypertonic urine following the administration of exogenous ADH. Treatment is generally directed at the underlying illness and ensuring an adequate fluid intake. Volume depletion by a thiazide diuretic can paradoxically decrease urinary output by reducing water delivery to collecting tubules. Sodium and protein restriction can similarly reduce urinary output.
Hypernatremia & Increased Total Body Sodium Content
This condition most commonly results from the administration of large quantities of hypertonic saline solutions (3% NaCl or 7.5% NaHCO3). Patients with primary hyperaldosteronism and Cushing syndrome may also have elevations in serum sodium concentration along with signs of increased sodium retention.
Clinical Manifestations of Hypernatremia
Neurological manifestations predominate in patients with symptomatic hypernatremia, and restlessness, lethargy, and hyperreflexia can progress to seizures, coma, and ultimately death. Symptoms correlate more closely with the rate of movement of water out of brain cells than with the absolute level of hypernatremia. Rapid decreases in brain volume can rupture cerebral veins and result in focal intracerebral or subarachnoid hemorrhage. Seizures and serious neurological damage are common, particularly in children with acute hypernatremia when plasma [Na+] exceeds 158 mEq/L. Chronic hypernatremia is usually better tolerated than the acute form. After 24 to 48 h, intracellular osmolality begins to rise as a result of increases in intracellular inositol and amino acid concentrations, and brain intracellular water content slowly returns to normal.
Treatment of Hypernatremia
The treatment of hypernatremia is aimed at restoring plasma osmolality to normal and correcting the underlying cause. Water deficits should generally be corrected over 48 h, as rapid correction (or overcorrection) can cause cerebral edema. Enteral free water administration is preferable when feasible, but a hypotonic intravenous solution such as 5% dextrose in water can also be used (see later discussion). Abnormalities in extracellular volume must also be corrected (Figure 49–4). Hypernatremic patients with decreased total body sodium should be given isotonic fluids to restore plasma volume to normal prior to treatment with a hypotonic solution. Hypernatremic patients with increased total body sodium should be treated with a loop diuretic along with intravenous 5% dextrose in water. The treatment of DI is discussed in the preceding section.
Algorithm for treatment of hypernatremia.
Rapid correction of hypernatremia can result in seizures, brain edema, permanent neurological damage, and even death. Serial Na+ osmolalities should be obtained during treatment. In general, decreases in plasma sodium concentration should not proceed at a rate faster than 0.5 mEq/L/h.
Example: A 70-kg man is found to have a plasma [Na+] of 160 mEq/L. What is his water deficit?
If one assumes that hypernatremia in this case represents water loss only, then total body osmoles are unchanged. Thus, assuming a normal [Na+] of 140 mEq/L and TBW content that is 60% of body weight:
To replace this deficit over 48 h, it is necessary to administer 5.3 L enteral free water in small amounts over 48 h, or, 5% dextrose in water intravenously, 5300 mL over 48 h, or 110 mL/h.
Note that this method ignores any coexisting isotonic fluid deficits, which if present should be replaced with an isotonic solution.
Hypernatremia has been demonstrated to increase the minimum alveolar concentration for inhalation anesthetics in animal studies, but its clinical significance is more closely related to the associated fluid deficits. Hypovolemia accentuates any vasodilation or cardiac depression from anesthetic agents and predisposes to hypotension and hypoperfusion of tissues. Decreases in the volume of distribution for drugs necessitate dose reductions for most intravenous agents, whereas decreases in cardiac output enhance the uptake of inhalation anesthetics.
Even mild serum sodium elevation is associated with increased perioperative morbidity, mortality, and hospital length of stay, and thus hypernatremia must not be ignored. Elective anesthetics should be postponed in patients with significant hypernatremia (>150 mEq/L) until the cause is established and total body sodium or TBW, or both, corrected.
HYPOOSMOLALITY & HYPONATREMIA
Hypoosmolality is nearly always associated with hyponatremia ([Na+] <135 mEq/L). Table 49–5 lists rare instances in which hyponatremia does not necessarily reflect hypoosmolality (pseudohyponatremia). Routine measurement of plasma osmolality in hyponatremic patients rapidly excludes pseudohyponatremia.
TABLE 49–5Causes of pseudohyponatremia.1 ||Download (.pdf) TABLE 49–5 Causes of pseudohyponatremia.1
Hyponatremia with a normal plasma osmolality
Marked glycine absorption during transurethral surgery
Hyponatremia with an elevated plasma osmolality
Administration of mannitol
Hyponatremia invariably reflects water retention from either an absolute increase in TBW or a loss of sodium in relative excess to loss of water. The kidneys’ normal capacity to produce dilute urine with an osmolality as low as 40 mOsm/kg (specific gravity 1.001) allows them to excrete over 10 L of free water per day if necessary. Because of this tremendous reserve, hyponatremia is nearly always the result of a defect in urinary diluting capacity (urinary osmolality >100 mOsm/kg or specific gravity >1.003—ie, limited ability of the kidneys to excrete free water). Rare instances of hyponatremia without an abnormality in renal diluting capacity (urinary osmolality <100 mOsm/kg) are generally attributed to primary polydipsia or reset osmoreceptors; the latter two conditions can be differentiated by water restriction.
Clinically, hyponatremia is best classified according to total body sodium content (Table 49–6). Hyponatremia associated with transurethral resection of the prostate is discussed in Chapter 32.
TABLE 49–6Classification of hypoosmolal hyponatremia. ||Download (.pdf) TABLE 49–6 Classification of hypoosmolal hyponatremia.
Decreased total body sodium content
Osmotic diuresis (glucose, mannitol)
Renal tubular acidosis
Normal total body sodium content
Increased total body sodium content
Congestive heart failure
Hyponatremia & Low Total Body Sodium
Progressive losses of both sodium and water eventually lead to extracellular volume depletion. As the intravascular volume deficit approaches 5% to 10%, nonosmotic ADH secretion is activated (see earlier discussion). With further volume depletion, the stimuli for nonosmotic ADH release overcome any hyponatremia-induced suppression of ADH. and preservation of circulatory volume takes place at the expense of plasma osmolality.
Fluid losses resulting in hyponatremia may be renal or extrarenal in origin. Renal losses are most commonly related to thiazide diuretics and result in a urinary [Na+] greater than 20 mEq/L. Extrarenal losses are typically gastrointestinal and usually are associated with a urinary [Na+] of less than 10 mEq/L. A major exception to the latter is hyponatremia due to vomiting, which can result in a urinary [Na+] greater than 20 mEq/L. In this situation, renal compensation for the associated metabolic alkalosis results in bicarbonaturia, with concomitant excretion of Na+ with HCO3 to maintain electrical neutrality in the urine; urinary chloride concentration, however, is usually less than 10 mEq/L.
Hyponatremia & Increased Total Body Sodium
Edematous disorders are characterized by an increase in both total body sodium and TBW. When the increase in TBW is relatively greater than the increase in total body sodium, hyponatremia occurs. Edematous disorders include congestive heart failure, cirrhosis, kidney failure, and nephrotic syndrome. Hyponatremia in these settings results from progressive impairment of renal free water excretion and generally parallels underlying disease severity. Pathophysiological mechanisms include nonosmotic ADH release and decreased delivery of fluid to nephron distal diluting segments (see Chapter 30).
Hyponatremia with Normal Total Body Sodium
Hyponatremia in the absence of edema or hypovolemia may be seen with glucocorticoid insufficiency, hypothyroidism, drug therapy, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH, also referred to as the syndrome of inappropriate diureses [SIAD]; Table 49–7). The hyponatremia associated with adrenal hypofunction may be due to co-secretion of ADH with corticotropin-releasing factor (CRF). Diagnosis of SIADH requires exclusion of other causes of hyponatremia and the absence of hypovolemia, edema, and adrenal, renal, or thyroid disease. Various malignant tumors, pulmonary diseases, and central nervous system disorders are commonly associated with SIADH. In most such instances, plasma ADH concentration is not elevated but is inadequately suppressed relative to the degree of hypoosmolality in plasma; urine osmolality is usually greater than 100 mOsm/kg and urine sodium concentration is greater than 40 mEq/L.
TABLE 49–7Causes of SIADH.1,2
Cerebral salt wasting (CSW) is a syndrome of inappropriate renal sodium wasting and hyponatremia with polyuria and hypovolemia that may be seen with intracranial disease, including brain tumors, subarachnoid hemorrhage, subdural hematoma, meningitis, and head trauma. Proposed mechanisms for this disorder include excess secretion of natriuretic peptides and altered sympathetic stimulation to the kidney. Both SIADH and CSW are characterized by elevated urine sodium concentration, low serum osmolality, and high urine osmolality. However, patients with SIADH are usually euvolemic or mildly hypervolemic, whereas patients with CSW are hypovolemic, and thus treatments for these two disorders are very different. The treatment of SIADH is free water restriction, and the treatment of CSW is volume and sodium replacement with normal or hypertonic saline.
Clinical Manifestations of Hyponatremia
Symptoms of hyponatremia are primarily neurological and result from an increase in intracellular water. Their severity is generally related to the rapidity with which extracellular hypoosmolality develops. Patients with mild to moderate hyponatremia ([Na+] >125 mEq/L) are frequently asymptomatic. Early symptoms are typically nonspecific and may include anorexia, nausea, and weakness. Progressive cerebral edema, however, results in lethargy, confusion, seizures, coma, and finally death. Serious manifestations of hyponatremia are generally associated with plasma sodium concentrations less than 120 mEq/L.
Patients with slowly developing or chronic hyponatremia are generally less symptomatic, probably because the gradual compensatory loss of intracellular solutes (primarily Na+, K+, and organic osmolytes) restores cell volume to near normal. Neurological symptoms in patients with chronic hyponatremia may be related more closely to changes in cell membrane potential (due to a low extracellular [Na+]) than to changes in cell volume.
Treatment of Hyponatremia
As with hypernatremia, the treatment of hyponatremia (Figure 49–5) is directed at correcting both the underlying disorder as well as the plasma [Na+]. Isotonic saline is generally the treatment of choice for hyponatremic patients with decreased total body sodium content. Once the ECF deficit is corrected, spontaneous water diuresis returns plasma [Na+] to normal. Conversely, water restriction is the primary treatment for hyponatremic patients with normal or increased total body sodium. More specific treatments such as hormone replacement in patients with adrenal or thyroid hypofunction and measures aimed at improving cardiac output in patients with heart failure may also be indicated. Demeclocycline (Declomycin, Declostatin), a tetracycline antibiotic that antagonizes ADH activity at the renal tubules, is often used as an adjunct in the treatment of SIADH when water restriction alone is insufficient.
Algorithm for treatment of hyponatremia.
Acute, symptomatic hyponatremia requires prompt treatment. In such instances, correction of plasma [Na+] to greater than 125 mEq/L is usually sufficient to alleviate symptoms and signs. The amount of NaCl necessary to raise plasma [Na+] to the desired value, the Na+ deficit, can be estimated by the following formula:
Na+ deficit = TBW × (Desired [Na+] – Present [Na+])
Excessively rapid correction of hyponatremia has been associated with demyelinating lesions in the pons (central pontine myelinolysis) and more generally in both pontine and extrapontine central nervous system structures (osmotic demyelination syndrome), resulting in both temporary and permanent neurological sequelae. The rapidity with which hyponatremia is corrected should be tailored to the severity of symptoms. The following correction rates have been suggested: for mild symptoms, 0.5 mEq/L/h or less; for moderate symptoms, 1 mEq/L/h or less; and for severe symptoms, 1.5 mEq/L/h or less.
Example: An 80-kg woman is lethargic and is found to have plasma [Na+] of 118 mEq/L. How much NaCl must be given to raise her plasma [Na+] to 130 mEq/L?
Na+ deficit = TBW × (130 − 118)
TBW is approximately 50% of body weight in females:
Na+ deficit = 80 × 0.5 × (130 − 118) = 480 mEq
Because normal (isotonic) saline contains 154 mEq/L, the patient should receive 480 mEq ÷ 154 mEq/L, or 3.12 L of normal saline. For a correction rate of 0.5 mEq/L/h, this amount of saline should be given over 24 h (130 mL/h).
Note that this calculation does not take into account any coexisting isotonic fluid deficits, which, if present, should also be replaced. More rapid correction of hyponatremia can be achieved by giving a loop diuretic to induce water diuresis while replacing urinary Na+ losses with isotonic saline. Even more rapid corrections can be achieved with intravenous hypertonic saline (3% NaCl). Hypertonic saline may be indicated in markedly symptomatic patients with plasma [Na+] less than 110 mEq/L. Three percent NaCl should be administered with caution, as it can precipitate pulmonary edema, hypokalemia, hyperchloremic metabolic acidosis, and transient hypotension; bleeding associated with prolongation of the prothrombin time and activated partial thromboplastin time has been reported.
Hyponatremia is the most common electrolyte disorder, and SIADH is its most common cause. Hyponatremia, in association with its underlying disorder(s), increases both perioperative morbidity and mortality. A plasma sodium concentration greater than 130 mEq/L is usually considered safe for patients undergoing general anesthesia. In most circumstances, plasma [Na+] should be corrected to greater than 130 mEq/L for elective procedures, even in the absence of neurological symptoms. Lower concentrations may result in significant cerebral edema that can be manifested intraoperatively as a decrease in minimum alveolar concentration or postoperatively as agitation, confusion, or somnolence. Patients undergoing transurethral resection of the prostate can absorb significant amounts of water from irrigation fluids (as much as 20 mL/min) and are at high risk for rapid development of profound acute water intoxication (see Chapter 32).