This chapter deals with electrolytes and diuretics. It thoroughly goes through pertinent facts about electrolytes such as sodium, potassium, calcium, phosphate, and magnesium. Particular attention is paid to hypo- and hypernatremia. Furthermore, diuretics is discussed.
Keywordselectrolytes, sodium, potassium, calcium, phosphate, magnesium, diuretics
Electrolyte concentrations are tightly controlled within physiologic ranges, which are essential for human health. The major electrolytes, sodium (Na + ), potassium (K + ), calcium (Ca 2+ ), phosphate (PO 4 3− ), and magnesium (Mg 2+ ), are critical to basic physiologic functions, including action potential generation, cardiac rhythm control, muscle contraction, and energy storage, among many others. Electrolytes, most notably Mg 2+ , are also important cofactors for the proper function of many crucial enzymes involved in DNA and protein synthesis and energy metabolism. Because appropriate electrolyte concentrations are so critical in human physiology, sophisticated homeostatic mechanisms maintain their concentrations within a narrow range.
When pathologic states alter electrolyte concentrations, severe physiologic aberrations can result. Therapies to increase or decrease electrolyte concentrations are thus important, especially in critical care. Sometimes electrolyte supplementation is necessary; in this context intravenous (IV) and oral preparations are viewed as drugs.
For each major electrolyte, we discuss physiologic roles, common pathologic alterations, and appropriate therapies, including the use of electrolytes as drugs. We also discuss the physiology and therapeutic considerations related to diuretics, a group of drugs that play an important role in perioperative medicine and have a pronounced influence on electrolyte homeostasis.
Sodium ion (Na + ) is the principal extracellular cation and solute and is essential for generation of action potentials in nervous and cardiac tissue. Pathologic increases or decreases in total body Na + are associated with corresponding increases or decreases in extracellular volume (ECV) and plasma volume (PV). Disorders of Na + concentration (i.e., hyponatremia and hypernatremia) usually result from relative excesses or deficits, respectively, of water. Regulation of total body Na + and plasma Na + concentration (Na + ) is accomplished primarily by the endocrine and renal systems ( Table 42.1 ). Secretion of aldosterone and antinatriuretic peptide control total body Na + . Antidiuretic hormone (ADH) is secreted in response to increased osmolality or decreased blood pressure, and primarily regulates Na + .
|Atrial natriuretic peptide|
|Na + altered by antidiuretic hormone|
|Intrinsic renal mechanisms|
|Phosphorus||Primarily renal mechanisms|
|Minor: parathyroid hormone|
|Magnesium||Primarily renal mechanisms|
|Minor: parathyroid hormone, vitamin D|
Hyponatremia, defined as Na + less than135 mEq/L or mM, is the most common electrolyte disturbance in hospitalized patients with a prevalence reaching 30%. It is associated with a high mortality. In most cases of hyponatremic hospitalized patients, total body Na + is either normal or increased. The most common clinical associations with hyponatremia include the postoperative state, acute intracranial disease, malignant disease, medications, and acute pulmonary disease.
The signs and symptoms of hyponatremia depend on both the rate and severity of the decrease in plasma Na + . Symptoms that can accompany severe hyponatremia (Na + < 120 mM) include anorexia, nausea, vomiting, cramps, weakness, altered level of consciousness, coma, and seizures. Acute central nervous system (CNS) manifestations relate to brain swelling. Because the blood-brain barrier is poorly permeable to Na + but freely permeable to water, a rapid decrease in plasma Na + promptly increases both extracellular and intracellular brain water. Because the brain rapidly compensates for changes in osmolality, acute hyponatremia produces more severe symptoms than chronic hyponatremia. The symptoms of chronic hyponatremia probably relate to depletion of brain electrolytes. Once brain volume has compensated for hyponatremia, rapid increases in Na + can lead to abrupt brain dehydration ( Fig. 42.1 ).
Hyponatremia can be classified as true hypoosmotic hyponatremia, pseudohyponatremia, or syndrome of inappropriate secretion of antidiuretic hormone (SIADH) ( Tables 42.2, 42.3, and 42.4 ). Pseudohyponatremia is an artifact associated with the use of flame photometry, now an obsolete technique, to measure plasma Na + in severely hyperproteinemic or hyperlipidemic patients. The current analytic method, direct potentiometry, directly measures Na + and is uninfluenced by plasma components such as proteins and lipids.
|Euvolemia (Urinary Sodium >20 mEq/L)|
|Normal Plasma Osmolality|
|Increased Plasma Osmolality|
Hyponatremia can be isotonic (plasma osmolality [P osm ] 280–295 mOsm/kg), hypotonic (P osm < 280 mOsm/kg), or hypertonic (P osm > 295 mOsm/kg). Calculated plasma osmolality is determined by the following formula:
P o s m = 2.0 × [ Na + ] + Glucose / 18 + BUN / 2.8 ,
Patients with disorders such as hypoproteinemia or hyperlipidemia that cause increased osmolality and pseudohyponatremia have an abnormal osmolality gap. These disorders highlight the importance of measuring plasma osmolality in hyponatremic patients. Hyponatremia with a normal or high serum osmolality results from the presence of a nonsodium solute, such as glucose or mannitol, that holds water within the extracellular space and results in dilutional hyponatremia. The presence of a nonsodium solute resulting in “factitious” hyponatremia can be inferred if measured osmolality exceeds calculated osmolality by more than 10 mOsm/kg. For example, plasma Na + decreases approximately 2.4 M for each 100-mg/dL rise in glucose concentration, with perhaps even greater decreases for glucose concentrations higher than 400 mg/dL.
In anesthesia practice, a common cause of hyponatremia associated with a normal osmolality is the absorption of large volumes of sodium-free irrigating solutions (containing mannitol, glycine, or sorbitol) during transurethral resection of the prostate. Neurologic symptoms are minimal if mannitol is used because the agent does not cross the blood-brain barrier and is excreted with water in the urine. In contrast, as glycine or sorbitol is metabolized, hypoosmolality can gradually develop and cerebral edema can appear as a late complication. Consequently, hypoosmolality is more important in generating symptoms than hyponatremia per se. The problem of excessive fluid absorption during transurethral resection of the prostate can be monitored by using small amounts of alcohol in the irrigating fluid; the level of alcohol can be detected in expired air as a quantitative measure of irrigating fluid absorption. True hyponatremia with a normal or elevated serum osmolality also can accompany renal insufficiency. BUN, included in the calculation of total osmolality, distributes throughout both ECV and intracellular volume (ICV). Calculation of effective osmolality (2 Na + + glucose/18) excludes the contribution of urea to tonicity and demonstrates true hypotonicity.
True hyponatremia ( Fig. 42.2 , Table 42.5 ) with low serum osmolality can be associated with a high, low, or normal total body Na + and PV. Therefore hyponatremia with hyposmolality is evaluated by assessing total body Na + content, BUN, serum creatinine (SCr), urinary osmolality, and urinary Na + . Hyponatremia with increased total body Na + is characteristic of edematous states—that is , congestive heart failure (CHF), cirrhosis, nephrosis, and renal failure. Aquaporin 2, the vasopressin-regulated water channel, is upregulated in experimental CHF and cirrhosis and decreased by chronic vasopressin stimulation. In patients with renal insufficiency, reduced urinary diluting capacity can lead to hyponatremia if excess free water is given.
|Extrarenal Na + Loss (FE Na < 1%, U Na < 20 mEq/L)||Renal Na + Loss (FE Na > 2%, U Na > 20 mEq/L)||(FE Na < 1%, U Na > 20 mEq/L)||(U Na < 20 mEq/L)|
|Glucocorticoid deficiency |
Psychogenic polydipsia (>15 L/day)
Beer potomania/malnutrition (alcoholism, anorexia)
The underlying mechanism of hypovolemic hyponatremia is secretion of ADH in response to volume contraction with ongoing oral or IV intake of hypotonic fluid. Angiotensin II also decreases renal free water clearance. Thiazide diuretics, unlike loop diuretics, promote hypovolemic hyponatremia by interfering with urinary dilution in the distal tubule of the nephron. Hypovolemic hyponatremia associated with a urinary Na + greater than 20 mM suggests mineralocorticoid deficiency, especially if serum K + , BUN, and SCr are increased.
The cerebral salt-wasting syndrome is an often severe, symptomatic salt-losing diathesis that appears to be mediated by brain natriuretic peptide and is independent of SIADH. Patients at risk include those with cerebral lesions caused by trauma, subarachnoid hemorrhage, tumors, and infection.
Euvolemic hyponatremia most commonly is associated with nonosmotic vasopressin secretion—for example, glucocorticoid deficiency, hypothyroidism, thiazide-induced hyponatremia, SIADH, and the reset osmostat syndrome. Total body Na + and ECV are relatively normal and edema is rarely evident. SIADH can be idiopathic but also is associated with CNS or pulmonary diseases (see Table 42.4 ). Euvolemic hyponatremia is usually associated with exogenous ADH administration, pharmacologic potentiation of ADH action, drugs that mimic the action of ADH in the renal tubules, or excessive ectopic ADH secretion. Tissues from some small cell lung cancers, duodenal cancers, and pancreatic cancers increase ADH production in response to osmotic stimulation.
At least 4.0 % of postoperative patients develop plasma Na + less than 130 mM. Although neurologic manifestations usually do not accompany postoperative hyponatremia, signs of hypervolemia are occasionally present. Much less frequently postoperative hyponatremia is accompanied by mental status changes, seizures, and transtentorial herniation, attributable in part to IV administration of hypotonic fluids, secretion of ADH, and other factors, including drugs and altered renal function, that influence perioperative water balance. Menstruating women are particularly vulnerable to brain damage secondary to postoperative hyponatremia. Smaller patients change plasma Na + more in response to similar volumes of hypotonic fluids. Based on a report of apparent postoperative SIADH in a 30-kg, 10-year-old girl, it has been suggested that children receive no sodium-free water perioperatively. Postoperative hyponatremia can develop even with infusion of isotonic fluids if ADH is persistently increased. Twenty-four hours after surgery, mean plasma Na + in patients undergoing uncomplicated gynecologic surgery decreased from 140 to 136 mM. Although the patients retained Na + perioperatively, they retained proportionately more water (an average of 1.1 L of electrolyte-free water). Careful postoperative attention to fluid and electrolyte balance can minimize the occurrence of symptomatic hyponatremia.
If both Na + and measured osmolality are below the normal range, hyponatremia is further evaluated by first assessing volume status using physical findings and laboratory data (see Fig. 42.2 and Table 42.5 ). In hypovolemic patients or edematous patients, the ratio of BUN to SCr should be greater than 20 : 1. Urinary Na + is generally less than 20 mM in edematous states and volume depletion, and greater than 20 mM in hyponatremia secondary to renal salt wasting or renal failure with water retention.
Criteria for the diagnosis of SIADH include hypotonic hyponatremia, urinary osmolality greater than 100 to 150 mmol/kg, absence of ECV depletion, normal thyroid and adrenal function, and normal cardiac, hepatic, and renal function. Urinary Na + should be greater than 20 mM unless fluids have been restricted. The diagnosis of SIADH is inaccurately applied to functionally hypovolemic postoperative patients, in whom, by definition, ADH secretion would be “appropriate.”
Treatment of hyponatremia associated with normal or high serum osmolality requires reduction of the elevated concentrations of the responsible solute. Uremic patients are treated by free water restriction or dialysis. Treatment of edematous (hypervolemic) patients necessitates restriction of both sodium and water. Therapy is directed toward improving cardiac output and renal perfusion and using diuretics to inhibit Na + reabsorption. In hypovolemic, hyponatremic patients, blood volume must be restored, usually by infusion of 0.9 % saline solution, and excessive Na + losses must be curtailed. Correction of hypovolemia usually results in removal of the stimulus for ADH release accompanied by a rapid water diuresis.
The cornerstone of SIADH management is free water restriction and elimination of precipitating causes. Water restriction, sufficient to decrease total body water (TBW) by 0.5 to 1.0 l/day, decreases ECV even if excessive ADH secretion continues. The resultant reduction in glomerular filtration rate (GFR) enhances proximal tubular reabsorption of salt and water, thereby decreasing free water reabsorption, and stimulates aldosterone secretion. As long as free water losses (i.e., renal, skin, gastrointestinal) exceed free water intake, serum Na + will increase. During treatment of hyponatremia, increases in plasma Na + are determined by both the composition of the infused fluid and the rate of renal free water excretion. Free water excretion can be increased by administering furosemide. However, the correction of hyponatremia continues to generate controversy. When plasma Na + is less than 130 mM or hyponatremia is present together with cerebral symptoms, it is recommended to immediately administer one or more IV boluses of 2 mL/kg of 3% NaCl. This should result in a prompt response and should be followed by boluses every 5 to 10 minutes as needed. Symptoms should disappear when plasma Na + has risen by 4 to 6 mM.
This approach differs from a previously advocated focus on a separation between acute and chronic causes for hyponatremia. Apart from the fact that this can be very difficult to distinguish based on history and physical examination, when hyponatremia is seriously symptomatic the problem must be addressed expeditiously. When cerebral function has been restored, there is an inadvertent risk of overcorrection with the risk of osmotic demyelination. There are no prospective studies of the absolute safe speed for correction of hyponatremia. Goals can be set to 8 mM in 24 hours, 14 mM in 48 hours, and 16 mM in 72 hours. A formula for predicting changes of plasma Na + is shown in the following equation:
[ N a + ] 2 = [ N a + ] 1 × T B W + Δ ( N a + + K + ) T B W + ΔTBW ,