Chapter 44. Fluid, Electrolyte, & Acid–Base Emergencies

The diagnosis of fluid and electrolyte disorders is complicated by the often-nonspecific symptoms and physical examination findings, which patients suffering from these disorders manifest. A thorough understanding of the homeostatic mechanisms that control fluid and electrolyte balance is essential to the accurate assessment and treatment of the wide variety of pathologies the emergency physician may encounter.

Approximately 60% of an adult male's body weight is composed of water (less in women and the elderly), of which 2/3 is intracellular and 1/3 is extracellular. Of the extracellular volume, 3/4 is in the interstitial compartment and 1/4 within the vasculature. Osmolality is maintained within a narrow range (285–295 mOsm) and is the same across all fluid compartments; it may be estimated using serum sodium, glucose, and blood urea nitrogen (BUN) values (see Appendix).

Shifts in volume, osmolality, and electrolyte concentrations can occur independently of each other and typically manifest in profoundly different ways. The severity of symptoms is usually contingent on how rapidly the shifts occur. Changes in volume are most readily apparent on the cardiovascular physical examination. Signs and symptoms attributable to changes in osmolality are primarily neurological, resulting from brain dehydration (in hyperosmolar states) or brain edema (in hypoosmolar states). Electrolyte changes are more variable and exert their effect primarily on cell membrane potential with resultant cardiac, neurologic, and musculoskeletal dysfunction. See Table 44–1 for a list of serum electrolytes and normal values.

Disorders of Serum Sodium Concentration

Hyponatremia

Essentials of Diagnosis

• Hyponatremia reflects a relative inability to excrete free water
• Symptoms relate to the rate of change
• Measure urine osmolality and sodium
• Review medications and assess thyroid and adrenal function
• Initial treatment is guided by the severity of symptoms and the patient's volume status

General Considerations

Hyponatremia is defined as a serum sodium below 136 mEq/L and is associated with a number of different drugs and disease processes. Hyponatremia may be hyper-, hypo-, or isotonic. Isotonic hyponatremia is the result of laboratory artifact due to a decreased water component of plasma such as may be seen in hyperlipidemia and hyperproteinemia. Newer ion-specific methods of laboratory analysis have essentially eliminated this as a cause of hyponatremia. Hypertonic hyponatremia results from the presence of solutes that do not freely cross cell membranes, such as mannitol and glucose (in the absence of insulin), and represents a hyperosmolar state. With prolonged hyperglycemia, moderation of the hyponatremia or even hypernatremia may result as an osmotic diuresis develops.

Most hyponatremia is hypotonic, representing an excess of total body water relative to total body sodium (which may be low, normal, or even high). In the absence of renal failure, increased levels of arginine vasopressin (AVP), from drugs, paraneoplastic syndromes, or other endocrine abnormalities, or rarely excess free water intake prevent the kidneys from excreting sufficient free water. Hypotonic hyponatremia can be associated with normal, increased, or decreased volume, and knowledge of the patient's urine sodium concentration and osmolality is invaluable in determining the underlying etiology (Figure 44–1).

Clinical Findings

Symptoms are rare with sodium above 125 mEq/L and when present reflect worsening cerebral edema, ranging from headache, nausea, vomiting, and mental status changes, culminating in seizures, coma, brain-stem herniation, and death. More severe symptoms are associated with a more rapid decrease in serum sodium. The clinician should correlate the measured serum sodium with the patient's presentation to eliminate spurious hyponatremia, such as that produced by a sample contaminated with a hypotonic infusion. In hyperglycemic states, every 100 mg/dL of glucose decreases the measured serum sodium value by 1.5–1.7 mEq/L, and the clinician should calculate the actual serum sodium accordingly.

Treatment

The urgency of treatment is dictated by the severity of symptoms and how abruptly the hyponatremia is thought to have developed. Correction of hyponatremia is controversial, but in acutely symptomatic patients even a 5% increase may be physiologically significant. In the presence of severe hyponatremia (sodium < 120 mEq/L and symptoms to include mental status changes, seizure, or coma), an infusion of 3% hypertonic saline solution (513 mEq/L) should be considered (see Appendix for formulas). The rate of rise of 1 mEq/L/h should be targeted for the first 3–4 hours or until symptoms resolve; otherwise, the rate of correction should not exceed 0.5 mEq/L/h. Simultaneous use of furosemide to limit expansion of the extracellular-fluid volume may be required. A new class of AVP receptor antagonists (the “vaptans”) has been approved for the treatment of euvolemic and hypovolemic hyponatremia, but experience with these agents in the ED is lacking. Resolution of symptoms, particularly in the elderly, may lag behind correction of the serum sodium, and frequent monitoring is important to avoid overcorrection.

Consideration should be given to thyroid and adrenal insufficiency, and replacement hormones given after appropriate laboratory samples have been obtained if indicated, and potassium replacement instituted if needed. Patients who do not require urgent treatment may be treated with fluid restriction and observation. Profoundly hypovolemic patients may be treated initially with fluid resuscitation using isotonic saline to prevent cardiovascular compromise. Emergency dialysis should be considered for patients with renal failure, volume overload, and severe hyponatremia.

Osmotic demyelination, the most feared consequence of too rapid correction, is rare at a rate of correction below 10–12 mEq/L/d. Alcoholics, hypokalemic patients, burn victims, and women taking thiazide diuretics are more at risk for this consequence. Symptoms of osmotic demyelination include dysarthria, dysphagia, spastic paresis, coma, and occasionally seizures. These symptoms may be delayed for 2–6 days after correction of the serum sodium and imaging by CT may be negative up to 4 weeks. Rapid reinduction of hyponatremia may be beneficial when this disorder is suspected.

Disposition

All patients with clinically significant hyponatremia should be hospitalized. ICU placement should be considered for those with severe mental status changes or seizures.

Hypernatremia

Essentials of Diagnosis

• Hypernatremia may result from the loss of pure water or hypotonic fluid, or rarely from salt gain
• Symptoms are primarily neurologic and those related to severe hypovolemia
• Measure urine osmolality and sodium concentration
• Use isotonic saline to treat volume deficits on an emergency basis, followed by hypotonic solutions to gradually replace free water deficits

General Considerations

Hypernatremia is defined as a serum sodium above 146 mEq/L, and unlike hyponatremia, it always represents a hyperosmolar state with cellular dehydration. It represents a relative excess of sodium to free water and may result from net water loss, either pure water or hypotonic fluid loss or sodium loading, usually accidental or iatrogenic (Table 44–2). Hypernatremia in outpatients is more common at the extremes of age or in debilitated patients. Although present in only 1% of hospitalized patients, it has a mortality approaching 60%. As with hyponatremia, the severity of symptoms is related to the rate at which they develop.

Clinical Findings

Symptoms from hypernatremia reflect CNS dysfunction and are more prominent with large or rapid changes in serum sodium. Infants with hypernatremia may have muscle weakness, restlessness, a high-pitched cry, lethargy, and coma. Elderly patients typically have few or no symptoms until the sodium is over 160 mEq/L. Loss of thirst and progressive decrease in level of consciousness are associated with worsening hypernatremia, but seizures are rare in the absence of aggressive rehydration. When sodium changes occur rapidly, traction on the cerebral vasculature from brain shrinkage may result in tearing with subarachnoid, intraparenchymal, and subdural bleeding. Patients may be clinically hyper-, hypo-, or euvolemic. Skin turgor may be normal despite intravascular volume depletion.

Evaluation of urine osmolality and sodium concentration is necessary to determine the underlying cause, particularly in hypovolemic patients. Hypovolemia with a urine sodium concentration less than 20 mEq/L is consistent with extrarenal losses. Urine osmolality over 400 mOsm/L represents intact renal free water conservation, while dilute urine (less than 250 mOsm/L) is associated with diabetes insipidus (see Chapter 41).

Treatment

In cases of circulatory compromise, volume deficits should be treated initially with isotonic saline. Otherwise, only hypotonic solutions should be used. In hypernatremia that has developed over a period of hours, rapid correction (∼1 mEq/L/h) does not increase the risk of convulsions or brain damage. When the rate of development is unknown, a rate of correction no greater than 0.5 mEq/L/h, or approximately 10 mEq per day, is recommended to avoid cerebral edema (see Appendix).

Disposition

Hospitalization is recommended for all symptomatic patients and patients with a sodium greater than 150 mEq/L. Patients with mild hypernatremia, an intact thirst mechanism, and close follow-up may be discharged home.

Disorders of Serum Potassium Concentration

Over 98% of the body's potassium is intracellular, making it the predominant intracellular electrolyte. Because of this, it is often difficult to make extrapolations regarding total potassium stores from serum potassium concentrations. Potassium is sensitive to changes in serum pH caused by the accumulation of mineral acids. Intracellular acidosis promotes the extrusion of potassium with resultant hyperkalemia. In addition to aldosterone, circulating hormones such as insulin and catecholamines also affect the movement of potassium between the serum and intracellular compartments. Symptoms related to changes in serum potassium are related to changes in cell membrane potential, affecting primarily the heart and muscles.

Hypokalemia

Essentials of Diagnosis

• Usually associated with diuretic therapy
• Symptoms are primarily neuromuscular and cardiac
• Assess acid–base status
• Replace potassium orally whenever possible; IV potassium may be given with caution in severe cases with appropriate monitoring

General Considerations

Hypokalemia, defined as a serum potassium below 3.5 mEq/L, is the most common electrolyte disturbance and may represent decreased total body stores of potassium or a shift of potassium into cells. A decrease in total body potassium is most often secondary to diuretic therapy but may also be from increased GI or renal losses, or, in the setting of alcoholism or malnutrition, decreased intake (see Table 44–3). Concurrent digitalis therapy exacerbates the cardiac effects of hypokalemia. Potassium deficiency commonly coexists with other electrolyte abnormalities, particularly magnesium, and may remain refractory to therapy until the other abnormalities are corrected.

Clinical Findings

Symptoms of hypokalemia range from mild weakness, ileus, and rhabdomyolysis to paralysis and lethal arrhythmias (see Table 44–4). The severity of symptoms is often related to how quickly the decrease in serum potassium develops. Obtaining a venous pH may be helpful in determining initial treatment. EKG changes are present in over 80% of people with a potassium below 2.7 and may progress rapidly from decreased T wave amplitude to torsades de pointes (see Table 44–5).

Treatment

On average, a decrease of 0.3 mEq/L in serum potassium is associated with a 100 mEq deficit in total body stores. Oral replacement using potassium chloride (20–40 mEq every 4 hours) is the preferred method for patients with mild symptoms who are able to tolerate oral intake. Higher doses should be avoided because of the risk of esophageal and gastric irritation or perforation in the presence of strictures. Potassium phosphate preparations may be used for patients with known phosphate deficiency, and potassium bicarbonate may be helpful in patients with severe metabolic acidosis.

For more severe symptoms and in patients with a serum potassium below 2.5, IV replacement is indicated. The concentration of potassium in IV solutions should not exceed 60 mEq/L (20 mEq/L if infusing through a peripheral line). More concentrated solutions are associated with greater pain at the infusion site and sclerosis of the veins. An IV infusion of 20 mEq/h is expected to produce an increase in the serum potassium of 0.25 mEq/h. In rare instances such as acute myocardial infarction with significant ventricular ectopy or in patients with paralysis of the respiratory muscles, rates of infusion as high as 40–100 mEq/h or more concentrated solutions may be indicated. Potassium should not be given in dextrose-containing solutions, as this may stimulate insulin release and result in worsening hypokalemia. All patients receiving IV potassium should have continuous cardiac monitoring, and it should never be given as a “push” because of the risk of precipitating life-threatening hyperkalemia.

Disposition

All patients with a serum potassium below 2.5 mEq/L should be hospitalized in a monitored setting. Patients with less severe hypokalemia may be discharged with oral replacement therapy and close follow-up.

Hyperkalemia

Essentials of Diagnosis

• Hyperkalemia is a true emergency
• Suspect hyperkalemia in patients with renal failure, diabetes, or those taking potassium supplements
• Symptoms are primarily neuromuscular and cardiac
• EKG findings may progress rapidly from peaked T waves to ventricular fibrillation
• Beware of spurious hyperkalemia
• Treatment stabilizes cardiac membranes, shifts potassium into cells, and removes potassium from the body

General Considerations

Hyperkalemia, defined as a serum potassium greater than 5.0 mEq/L, is more rare but more immediately life threatening than hypokalemia. It may rarely result from increased potassium intake but more commonly results from decreased renal excretion or transmembrane shift of intracellular potassium (see Table 44–6). Drugs that interfere with the renin-angiotensin-aldosterone system, such as ACE inhibitors or spironolactone, may result in hyperkalemia, as may drugs such as trimethoprim and triamterene that block secretion of potassium in the distal collecting duct. Digitalis toxicity may result in hyperkalemia through inhibition of the distal-collecting duct Na+/K+ ATP-ase.

Pseudohyperkalemia is frequently encountered and should be suspected when patients with normal renal function and no other evident precipitating cause for true hyperkalemia present with marked elevation in measured serum potassium. Hemolysis, thrombocytosis, marked leukocytosis, prolonged tourniquet time, and long delays between obtaining the lab specimen and analysis may result in release of intracellular potassium within the specimen; analysis of plasma potassium through a specimen collected in a heparinized tube may help differentiate true versus pseudohyperkalemia, with a difference of greater than 0.3 mEq/L suggestive of pseudohyperkalemia.

Clinical Findings

Symptoms attributable to hyperkalemia are nonspecific and include muscular weakness, fatigue, paresthesias, palpitations, and cardiac arrhythmias. EKG changes may progress rapidly from peaked T waves to QRS widening and ventricular fibrillation (see Table 44–7 and Figure 44–2); however, the presence of EKG changes poorly sensitive for a serum potassium over 6.0 mEq/L and may be absent in up to 80% of patients with significant hyperkalemia. Hyperkalemia is commonly associated with metabolic acidosis, and a venous blood gas may be helpful in guiding treatment. Evaluation of renal function and serum electrolytes is helpful in identifying contributing causes.

Treatment

Emergency treatment of hyperkalemia is warranted for true hyperkalemia exceeding 6.0 mEq/L or in the presence of any EKG changes consistent with hyperkalemia. The goals of therapy are aimed at stabilizing membrane potential, moving potassium intracellularly, and eliminating potassium from the body. Caution should be exercised in patients with conditions such as diabetic ketoacidosis (DKA), in which total body potassium may actually be low and concurrent correction of the acid–base disorder with overly aggressive therapy for hyperkalemia may result in hypokalemia.

Membrane Stabilization

Patients with EKG changes or potassium over 7.0 should receive IV calcium, which directly antagonizes the effect of potassium on cardiac membrane potential. Both calcium gluconate and calcium chloride are available as 10% solutions, although calcium chloride contains three times as much available calcium and is more irritating if it extravasates and may worsen acidosis. For these reasons, calcium gluconate is preferred; 10 mL may be given IV over 2–5 minutes and repeated in 10 minutes if there is no effect on the EKG. Effects may be seen within 1–3 minutes and last 30–60 minutes. In patients with hyper-kalemia associated with digoxin toxicity, calcium administration should be avoided since calcium potentiates the myocardial toxicity of digoxin. Hypertonic saline may be used in hyperkalemic patients with significant hyponatremia as well.

Intracellular Shift

Ten units of regular insulin may be given IV along with 50 mL of D50 (to avoid precipitating hypoglycemia, if necessary) to promote cellular uptake of potassium, with onset within 20 minutes and peak effect between 30 and 60 minutes. Ten to twenty milligrams of nebulized albuterol (or 0.5 mg IV) may also be used, with a slightly delayed onset and peak effect compared to insulin. Infusion of sodium bicarbonate alone has a variable effect and should not be used as monotherapy (particularly in dialysis patients), but it has been shown to potentiate the potassium-lowering effects of insulin and β-agonist therapy.

Potassium Elimination

Direct elimination of potassium from the body by methods other than dialysis is the slowest method of reducing serum potassium and should not be used alone in the presence of significant hyperkalemia. Sodium polystyrene sulfonate may be given orally or as an enema in a dose of 25–50 g. The use of sorbitol as a laxative has been associated with intestinal necrosis and perforation, particularly in postoperative patients, and other laxatives may be preferable. Patients with intact renal function may benefit from therapy with potassium-losing diuretics. Dialysis should be considered in patients with renal failure or unstable patients, following institution of the above measures.

Disposition

All patients with hyperkalemia requiring treatment should be admitted to a monitored setting.

Disorders of Serum Calcium Concentration

Calcium is required for a large number of physiologic processes ranging from nerve conduction to blood coagulation. Calcium is commonly reported in mg/dL, which may be converted to mmol by dividing by 4 or to mEq by dividing by 2. Ninety-eight percent of calcium is bound to bone, and the regulation of extracellular calcium concentrations within the narrow range of 8.5–10.5 mg/dL is complex. Calcitonin, parathyroid hormone (PTH), vitamin D, phosphate, and calcium itself interact through a number of interlocking feedback loops to exert effects on the renal tubules, intestine, and bones.

Serum calcium is approximately 40% protein bound and 10% complexed with organic anions, leaving only 50% ionized. This is the physiologically active portion of serum calcium, which is highly sensitive to changes in pH. Rapid changes in pH may result in symptomatic hypo- or hypercalcemia even with normal serum calcium. As the serum pH increases, more calcium is bound, leaving a lower fraction available for use. Conversely, acidemia increases the amount of calcium available, with a change of 0.1 in pH roughly corresponding to a change in ionized calcium of 0.05 mmol/dL. Also, 1 mg/dL of albumin binds 0.8 mg/dL (0.2 mmol/dL) of calcium, which may be used to estimate expected changes in serum calcium in the setting of hypoalbuminemia; however, there is wide variability, and direct measurement of ionized calcium is preferable to calculation whenever hypo- or hypercalcemia is suspected.

Hypocalcemia

Essentials of Diagnosis

• Occurs often in critically ill patients, although rarely life-threatening in itself
• Usually asymptomatic until severe
• Neuromuscular and respiratory symptoms predominate
• Often associated with disorders of magnesium and phosphate
• Always check serum phosphate before replacing calcium IV
• Use caution in giving IV calcium to patients taking digoxin

General Considerations

Hypocalcemia is defined as an ionized calcium less than 1.1 mmol/L, although symptoms are uncommon until the ionized calcium falls below 0.7 mmol/L. Patients with low serum calcium may have a normal ionized calcium. Hypocalcemia may develop gradually from decreased intake or absorption and is commonly associated with decreased PTH and vitamin D levels. It may also be seen with “hungry bone” syndrome, which results after parathyroidectomy for hyperparathyroidism. Hyperphosphatemia and hypomagnesemia commonly coexist with hypocalcemia. More acute changes in calcium may result from shifts in serum pH and the increased concentration of organic anions, such as citrate in the case of massive transfusion or fatty acids in acute pancreatitis. Up to 50% of critically ill patients, particularly those in sepsis, will have hypocalcemia.

Clinical Findings

Symptoms of acute hypocalcemia are primarily neuromuscular, including circumoral numbness, paresthesias, and carpopedal spasm, progressing to tetany, laryngospasm, and seizures (see Table 44–8). Skeletal muscle fasciculations, Chvostek's and Trousseau's signs, and hyperreflexia may be evident on physical examination. Hypocalcemia that develops more slowly may manifest primarily with weakness, irritability, and neuropsychiatric symptoms. Prolongation of the QTc interval without changes in morphology or other intervals is the most common EKG finding in hypocalcemia. Torsades de pointes with hypocalcemia is less common than with hypokalemia or hypomagnesemia.

Evaluation of the patient with hypocalcemia should include measurement of other serum electrolytes (particularly magnesium, phosphate, and potassium), renal function, serum albumin, and a venous or arterial blood gas to evaluate the patient's acid–base status.

Treatment

Asymptomatic hypocalcemia rarely progresses to a life-threatening condition. Even mild symptoms due to hypocalcemia warrant further evaluation and treatment, however, because of the potential for significant compromise should the hypocalcemia worsen. Initial treatment is with IV calcium gluconate, which should be given slowly to avoid serious cardiac dysfunction (20 mL over 10–20 minutes, followed by infusion of 0.5–1.5 mg/kg/h of elemental calcium in dextrose or saline over 4–6 hours). Slower rates should be used in patients on digoxin. In the setting of hypomagnesemia, symptoms may remain refractory until the serum magnesium is also corrected. Hypocalcemia with markedly elevated phosphate (over 6 mg/dL) should not be treated with supplemental calcium to avoid the risk of metastatic calcification; initial treatment should focus on eliminating phosphate (see the Hyperphosphatemia section later in this chapter). Patients with mild or asymptomatic hypocalcemia may be treated with oral supplementation.

Disposition

Patients with acute or symptomatic hypocalcemia should be admitted to a monitored setting. Patients with chronic, asymptomatic hypocalcemia may be discharged with oral calcium supplements and followed up on an outpatient basis.

Hypercalcemia

Essentials of Diagnosis

• Usually caused by malignancy or hyperparathyroidism
• Symptoms are primarily neuromuscular and renal
• Volume replacement/expansion is primary therapy
• Treatment promotes calcium excretion, inhibits osteoclast activity, and decreases calcium absorption

General Considerations

Hypercalcemia is defined as a serum calcium over 11 mg/dL. As with most electrolyte disorders, the rate at which the hypercalcemia develops is an important determinant of the severity of symptoms. Although a number of different conditions may result in hypercalcemia, most symptomatic cases result from hyperparathyroidism or malignancy (see Table 44–9). Milk-alkali syndrome due to the use of calcium carbonate supplements for osteoporosis, dyspepsia, or hyperphosphatemia associated with chronic renal failure is an emerging cause of hypercalcemia. Rarely, hyperalbuminemia (such as from dehydration) or paraproteinemia may elevate the measured serum calcium value, and measurement of the ionized calcium will be beneficial. Similarly, hypoalbuminemia may partially mask an elevated ionized calcium and result in symptomatic hypercalcemia even at “normal” serum calcium values.

Clinical Findings

Most symptoms of hypercalcemia are mild and nonspecific, including fatigue, abdominal pain, anorexia, weakness, depression, vomiting, and constipation. Severe hypercalcemia may cause acute pancreatitis, and peptic ulcer disease secondary to prolonged hypercalcemia is also common. With ionized calcium concentrations above 3.0 mmol/L, cognitive dysfunction becomes more prominent, and above 4.0 mmol/L psychosis, stupor, and coma are expected. Although a shortened QTc interval may be seen on EKG, hemodynamically significant arrhythmias are rare.

Treatment

Treatment should be initiated for all patients with clinically significant symptoms. Moderate to severe hypercalcemia (ionized calcium greater than 3 mmol/L) warrants emergency treatment, even if asymptomatic. Specific therapy may be instituted if a precipitating cause is identified; however, general measures aimed at reducing serum calcium levels should be initiated at the same time. Modes of therapy for hypercalcemia consist of promoting calcium excretion, stabilizing or increasing deposition of calcium in the bones, and decreasing dietary uptake. Patients with renal insufficiency or those in whom the previous measures are ineffective may benefit from dialysis.

Promoting Calcium Excretion

Most patients with severe hypercalcemia are profoundly volume depleted from hypercalcemia-induced nephrogenic diabetes insipidus, and initial therapy should focus on replacing volume deficits with isotonic saline until the patient is clinically euvolemic. This will help induce calciuresis by increasing the glomerular filtration rate. After extracellular volume status is normalized, a loop diuretic may be used to promote further urinary excretion of calcium. Thiazide diuretics promote calcium resorption and should be avoided.

Bone Calcium Stabilization

Bisphosphonates such as pamidronate or zoledronate inhibit osteoclast activity and indirectly stimulate osteoblasts, promoting the deposition of calcium. Their maximum effect is delayed 2–4 days but lasts up to 4 weeks, and both are well tolerated when given as IV infusion. Pamidronate may be given as 60–90 mg in 500 mL isotonic saline over 1–2 hours. Zoledronate (4 mg) may be given IV over 15 minutes and is more effective than pamidronate at reducing serum calcium. Calcitonin (4 IU/kg given SQ or IM every 12 hours) may be used in conjunction with bisphosphonates and has an additive effect, although tachyphylaxis often develops within 2–3 days and it is only effective in 60–70% of patients. It works more rapidly than the bisphosphonates and should be reserved for more severe cases of hypercalcemia. Because of the potential for severe toxicity and the development of second-generation bisphosphonates, the use of mithramycin is not recommended.

Decreasing Absorption

Corticosteroids (hydrocortisone 200–300 mg/d IV or prednisone 20–40 mg/d PO) are effective at reducing vitamin D-mediated absorption of calcium from the GI tract and are particularly valuable in hypercalcemia associated with lymphoma and granulomatous diseases. Onset of action is within 3–5 days.

Disposition

Patients with significant symptoms should be hospitalized and consideration given to hospitalization for all patients with an ionized calcium above 3.0 mmol/L regardless of symptoms. Less severe cases may be discharged with close follow-up.

Disorders of Serum Phosphorus Concentration

Phosphate is present primarily in bone and skeletal muscle, with less than 1% of total body phosphate present in plasma. In addition to being essential to bone mineralization, it is also important in a large number of cellular functions, particularly energy metabolism. Approximately 15% of serum phosphate is protein bound, and serum levels may not reflect total body stores because of intracellular shift.

Hypophosphatemia

Essentials of Diagnosis

• Hypophosphatemia is often asymptomatic unless severe and commonly occurs along with disorders of calcium, magnesium, and potassium
• Assess acid–base status
• Oral replacement is preferred and should be initiated even in asymptomatic patients
• IV replacement may be used cautiously in severely symptomatic patients, with frequent monitoring of other electrolytes

General Considerations

Hypophosphatemia is defined as a serum phosphate below 2 mg/dL. It is typically asymptomatic unless it develops rapidly and may result from any combination of decreased intestinal absorption, increased urinary excretion, or intracellular shift (see Table 44–10). Acute respiratory alkalosis and glucose ingestion with insulin release are associated with intracellular shift. Effects on mineralization are seen more chronically, with phosphate-dependent energy pathways and 2,3-DPG formation impaired acutely.

Clinical Findings

Clinical findings in hypophosphatemia are nonspecific, reflecting the wide range of organs affected. Rhabdomyolysis, seizures, obtundation, coma, depressed cardiac contractility, ileus, dysarthria, and respiratory failure secondary to diaphragmatic weakness have been reported. With severe hypophosphatemia (below 0.5 mg/dL), hemolysis and impaired white blood cell and platelet function may occur.

Treatment

Phosphate replacement is indicated in patients with decreased serum phosphate regardless of symptoms. Oral supplementation is safe and preferred in almost all cases. Milk contains 1 mg of phosphate per milliliter, or oral formulations containing sodium or potassium phosphate are available. For severe symptomatic hypophosphatemia, IV infusion of sodium or potassium phosphate at a rate not to exceed 2.5 mg/kg over 6 hours may be initiated. Frequent monitoring of serum calcium, phosphate, potassium, and magnesium should be undertaken to avoid metastatic calcification from too rapid correction.

Disposition

Hospitalization is advised for all patients with a serum phosphate below 2.0 mg/dL. Patients not hospitalized should have prompt outpatient follow-up.

Hyperphosphatemia

Essentials of Diagnosis

• Hyperphosphatemia is often associated with renal disease or hypoparathyroidism
• Increased phosphate may be a manifestation of tumor lysis or rhabdomyolysis
• Initial treatment consists of volume expansion and using insulin and glucose to shift phosphate into cells

General Considerations

Hyperphosphatemia is defined as a serum phosphate greater than 5 mg/dL (7 mg/dL in children and the elderly due to increased bone turnover in these age groups). It most commonly results from renal failure but may also be seen with hypoparathyroidism, exogenous loading of phosphate or vitamin D, tumor lysis syndrome, rhabdomyolysis, and acidosis. Pseudohyperphosphatemia may result from hyperglobulinemia, hypertriglyceridemia, hyperbilirubinemia, and hemolysis.

Clinical Findings

Acutely, symptoms from hyperphosphatemia itself are rare and commonly referable to hypocalcemia and hyperkalemia. Chronic hyperphosphatemia may result in metastatic calcification, hyperparathyroidism, and renal dystrophy.

Treatment

Acute hyperphosphatemia should be treated aggressively. In patients with normal renal function, volume expansion using isotonic saline coupled with acetazolamide (15 mg/kg, 500 mg in an average adult) will promote phosphate excretion but requires careful monitoring to avoid lowering serum calcium as well. IV insulin and glucose may also be used as with hyperkalemia to move phosphate into the cells. Dialysis is indicated in patients with renal failure. For hyperphosphatemia that has developed chronically, the primary focus of treatment is reducing intestinal absorption by decreasing protein intake and using phosphate-binding antacids. In patients with renal failure, calcium-containing salts are preferred to reduce the risk of aluminum toxicity.

Disposition

Admission is more commonly indicated by the precipitating cause rather than strictly by hyperphosphatemia itself.

Disorders of Serum Magnesium Concentration

Magnesium is primarily an intracellular cation and is important in enzymatic regulation, muscle contractility, and synaptic transmission within the nervous system. Serum concentrations are regulated primarily by the kidney. Because most intracellular magnesium is bound, concentrations are tightly regulated even in the face of large variations in extracellular concentration.

Hypomagnesemia

Essentials of Diagnosis

• Frequently associated with disorders of calcium, potassium, and phosphate
• Common in malnourished patients and those with renal disease
• Symptoms are primarily neuromuscular and similar to those seen with hypocalcemia
• Oral replacement is preferred except in severe symptomatic cases

General Considerations

Hypomagnesemia is defined as a serum magnesium concentration below 1.5 mEq/L and is very common, occurring in 12% of hospitalized patients and almost 2/3 of patients admitted to the ICU. Symptoms are rare until serum concentrations fall below 1 mEq/L. It may result from a number of conditions that produce decreased intake, decreased GI absorption, or increased GI or renal loss (see Table 44–11). Hypokalemia and hypocalcemia frequently occur along with hypomagnesemia, as does metabolic alkalosis.

Clinical Findings

Clinical manifestations of hypomagnesemia are nonspecific and may be attributable to concurrent hypocalcemia or hypokalemia. Neurologic irritability with tremor, clonus, hyperreflexia, and tetany may occur with serum concentrations below 0.8 mEq/L, ultimately progressing to confusion and convulsions. Although there is no set of EKG findings consistently associated with decreased magnesium, both ventricular and supraventricular dysrhythmias appear to be potentiated. Prolongation of the QTc interval may occur secondary to coexistent hypokalemia or hypocalcemia.

Treatment

Correction of other electrolyte abnormalities, particularly calcium and potassium, may be necessary in addition to replacing magnesium. Oral replacement is preferred in patients with mild symptoms and may be accomplished with either magnesium oxide or magnesium gluconate. Parenteral therapy is indicated for patients with symptomatic hypomagnesemia and tetany or seizures, or in the presence of arrhythmias. A typical regimen is 2 g of magnesium sulfate in a 20% solution infused over 20 minutes followed by 1 g IV every 6 hours. Too rapid administration of magnesium may result in apnea secondary to transient paralysis of the respiratory muscles from hypermagnesemia. This may be reversed by the administration of calcium gluconate. In patients with renal failure, doses of magnesium should be reduced by half.

Disposition

Patients with symptomatic hypomagnesemia require admission. Asymptomatic patients may require admission for comorbid illnesses or may otherwise be discharged home with close follow-up.

Hypermagnesemia

Essentials of Diagnosis

• Symptoms are rare until magnesium levels are severely elevated
• Usually secondary to renal failure or excess magnesium intake
• Calcium gluconate can be used to reverse respiratory paralysis until forced diuresis or dialysis lowers serum magnesium levels

General Considerations

Hypermagnesemia is defined as a serum magnesium concentration over 3 mEq/L. It is rare, and typically results from excess ingestion of magnesium-containing antacids or laxatives. Patients with renal failure, bowel disorders, those requiring parenteral hyperalimentation, and the elderly are most at risk.

Clinical Findings

Hypermagnesemia is frequently asymptomatic until magnesium levels are severely elevated. With progressive elevation of the magnesium concentration, patients may experience nausea, vomiting, hypotension, confusion, muscle weakness, lethargy, loss of deep tendon reflexes, coma, and death secondary to respiratory paralysis. EKG changes include bradycardia, AV block, lengthening of the PR interval, QRS widening, and decreased P wave voltage with peaking of the T waves.

Treatment

Calcium gluconate may be used as a temporizing measure in cases of impending respiratory paralysis. Patients with normal renal function should undergo forced diuresis with isotonic saline and furosemide to promote renal excretion. Dialysis is indicated for severe hypermagnesemia and renal insufficiency.

Disposition

All patients with hypermagnesemia require admission.

Emergency physicians frequently encounter critically ill patients with acid–base disorders, and an accurate understanding of the underlying physiology behind these derangements and the body's attempt to compensate for them is essential to appropriately manage these patients.

Definitions

Hydrogen ion concentration is typically not expressed directly but rather in terms of pH. Normal blood pH ranges from 7.36 to 7.44, with deviations above this range referred to as alkalemia and deviations below referred to as acidemia. Changes in [H+] may result from changes in volatile (Pco2) or nonvolatile (sulfuric, lactic, etc.) acids. An acidosis is any condition that increases the amount of acid in the blood and may be further characterized as respiratory (increased volatile acid) or metabolic (increased nonvolatile acid). Similarly, an alkalosis reduces the amount of acid in the blood and may also be characterized as respiratory or metabolic.

Several different buffer systems exist to help maintain a serum pH close to 7.4. The most important extracellular buffer system is the bicarbonate–carbonic anhydrase system, which converts CO2 from cellular metabolism to carbonic acid that subsequently dissociates into H+ and bicarbonate.

An isolated metabolic or respiratory process results in a primary acid–base disorder, and multiple processes result in a mixed acid–base disorder. Metabolic processes affect bicarbonate concentration, and respiratory processes affect Pco2. As the serum pH is shifted away from the normal range by a primary acid–base disorder, compensatory processes begin that attempt to restore a normal pH. A metabolic acidosis or alkalosis is compensated by changes in ventilation and a respiratory acidosis or alkalosis is compensated by adjusting renal acid excretion. These compensatory mechanisms will shift blood pH toward normal. In primary acid–base disorders, the underlying disorder will be evident from examination of the pH, Pco2, and serum bicarbonate (see Table 44–12).

Respiratory compensation for primary metabolic disorders begins within minutes as chemoreceptors sense the change in extracellular pH and signal the respiratory center to change minute ventilation. In a primary metabolic acidosis, the acidemia stimulates an increase in minute ventilation and subsequent decrease in Pco2; conversely, a metabolic alkalosis results in hypoventilation and increased Pco2. Renal compensation for primary respiratory disorders does not begin in earnest until after 6–12 hours of sustained acidemia or alkalemia. In a primary respiratory acidosis, the kidneys increase bicarbonate synthesis, excrete more protons, and reclaim more bicarbonate from the proximal tubule. Alkalemia promotes the retention of H+ and increased bicarbonate excretion. Compensatory mechanisms may take several days to reach maximal effect, and with the exception of compensation for chronic respiratory alkalosis never restore the pH to normal. The timing and limits of compensation are detailed in Table 44–13. A normal pH in the setting of an acid–base disturbance should alert the clinician to the presence of a mixed acid–base disorder.

Evaluation of Acid–Base Disorders

The patient's history and physical examination often provide important clues to the presence and etiology of acid–base disorders and are particularly valuable in the case of mixed disorders. Beyond the history and physical examination, initial assessment of acid–base disorders requires an electrolyte panel and blood gas. Values obtained via venous blood gas sampling (with the exception of Po2) are quite similar to those obtained via arterial sampling; pH is typically 0.01–0.03 lower, Pco2 is 6 mm Hg higher, and bicarbonate is 2 mEq/L higher in venous samples when compared to arterial samples. “Arterialization” of the venous blood specimen by warming the hand at 45°C for 10 minutes eliminates even these differences. Because of the decreased pain and morbidity associated with venous sampling, use of venous blood should be considered when oxygenation is not a concern.

The first step in analyzing the laboratory data in acid–base disorders is to ensure the internal consistency of that data using the Henderson-Hasselbalch equation (see Appendix). Following this, an anion gap should be calculated by adding the serum [Cl−] and [HCO3−] and subtracting this sum from the serum [Na+]. The anion gap represents the negative charge from unmeasured serum proteins and averages 10–12 mEq/L. The delta anion gap is the difference between the calculated anion gap and a normal anion gap, and when compared with the change in bicarbonate can be an important clue to the presence of a mixed disorder.

To determine the primary disorder, first examine the bicarbonate. Increased bicarbonate reflects either a primary metabolic alkalosis or metabolic compensation for a primary respiratory acidosis. Examination of the pH will then reveal the primary disorder: an elevated pH indicates a primary metabolic alkalosis, and a decreased pH indicates a primary respiratory acidosis. Decreased bicarbonate may result from a primary metabolic acidosis or as metabolic compensation for a respiratory alkalosis; decreased pH indicates a metabolic acidosis and increased pH indicates a respiratory alkalosis. Normal pH in the presence of either increased or decreased bicarbonate indicates a mixed disorder. In primary disorders, Pco2 and bicarbonate should deviate in the same direction, while in mixed disorders they deviate in opposite directions. Depending on the clinical setting, examination of serum and urine osmolality and urine electrolytes may be warranted to fully characterize the nature of the disorder.

Clinical Acid–Base Disorders

Respiratory Acidosis

Essentials of Diagnosis

• Impairment in alveolar ventilation results in hypercapnia
• Alteration in consciousness may result
• Treatment is aimed at improving ventilation by treating the underlying disorder

General Considerations

Respiratory acidosis is defined as an elevated Pco2 (>45 mm Hg) and a decrease in serum pH below 7.36. Any condition that results in alveolar hypoventilation may cause respiratory acidosis (see Table 44–14).

Clinical Findings

The hallmark of respiratory acidosis is an alteration in level of consciousness. The characteristic features of hypercapnia range from fatigue, irritability, headache, confusion, stupor, and obtundation to coma and are dependent on the severity and chronicity of the hypercapnia. A Pco2 of 70 may result in coma when secondary to an acute respiratory acidosis, while a person with chronic respiratory acidosis may tolerate Pco2 levels higher than this without a decrease in mental status.

Physiology

Acute Respiratory Acidosis

Acutely, the increased protons resulting from a respiratory acidosis are buffered by intracellular proteins. This results in a rise in [HCO3−] of 1 mEq/L for every 10 mm Hg increase in Pco2 up to a maximum [HCO3−] of 30 mEq/L and a decrease in pH of 0.08. This compensation is complete within minutes and no further compensation is possible until renal excretion of acid begins, which may take 72–96 hours.

Chronic Respiratory Acidosis

Chronic respiratory acidosis commonly results from COPD and extreme obesity. Renal compensation reaches a steady state after 3–4 days and involves the excretion of chloride in addition to acid, with retention of bicarbonate. An increase in the Pco2 of 10 mm Hg is expected to result in an increase in [HCO3−] of 3.5 mEq/L (to a maximum of 45 mEq/L) and a decrease in pH of 0.03.

Treatment and Disposition

Treatment consists primarily of reversing and stabilizing the underlying process that generated the respiratory acidosis. Bronchodilators, reversal of opioids, and support of ventilation using either BiPAP or intubation may be warranted depending on the clinical picture. Care should be taken not to decrease the Pco2 too rapidly in the setting of chronic respiratory acidosis, as the shift in pH may result in electrolyte abnormalities with dysrhythmias or seizure. Patients with acute respiratory acidosis requiring therapy should be admitted. Admission for patients with chronic respiratory acidosis is more commonly warranted by other findings such as hypoxemia.

Respiratory Alkalosis

Essentials of Diagnosis

• Hypocapnia may be generated by many common causes
• Chronic respiratory alkalosis may be completely compensated
• Treat the underlying cause

General Considerations

Respiratory alkalosis is defined as a Pco2 below 35 mm Hg with an increase in serum pH above 7.44. Acutely, respiratory alkalosis is most commonly caused by hyperventilation secondary to other causes (see Table 44–15). These causes may reduce Pco2 to 25–35 mm Hg, with further decreases resulting from concurrent metabolic acidosis or hypoxia.

Clinical Findings

The clinical findings of respiratory alkalosis vary depending on the severity and acuity of the process. Acutely, symptoms attributable to hypocalcemia (such as circumoral and digital paresthesia and carpopedal spasm) may occur from the rapid shift in pH. More severe hypocapnia may result in cerebral vasoconstriction with lightheadedness, dizziness, confusion, and altered consciousness. Chronically, respiratory alkalosis may result in hypophosphatemia and a lowered seizure threshold.

Physiology

Acute Respiratory Alkalosis

Compensation for acute hypocapnia begins within minutes and involves the movement of protons from the intracellular to the extracellular space. For every decrease in Pco2 of 10 mm Hg, [HCO3−] should decrease by 2.5 mEq/L and pH should increase by 0.08.

Chronic Respiratory Alkalosis

Renal compensation for chronic respiratory alkalosis results in decreased proton excretion and the retention of chloride for bicarbonate. Chronically, a decrease in Pco2 of 10 mm Hg will result in a decrease in [HCO3−] of 5 mEq/L. With prolonged hypocapnia (2 weeks or more), pH may be normal.

Treatment and Disposition

Treatment for respiratory alkalosis focuses on treating the underlying disorder, with disposition based on the precipitating cause rather than the alkalosis itself.

Metabolic Acidosis

Essentials of Diagnosis

• Commonly divided into anion gap and nongap causes
• Cardiovascular effects are most immediately life-threatening
• Calculate the anion gap and delta gaps
• Use Winter's formula to identify respiratory compensation
• Treat the underlying cause

General Considerations

Metabolic acidosis occurs due to an imbalance between the plasma concentration of H+ and HCO3− and is defined as a decrease in [HCO3−] to below 22 with a decrease in pH below 7.36. It may result from overproduction of organic acids (most commonly lactate or ketones), loss of bicarbonate through intestinal or renal wasting, or the inability to excrete acids from normal metabolism or toxin ingestion.

Clinical Findings

Metabolic acidosis results in a variety of impairments regardless of the underlying etiology (see Table 44–16). The anion gap is commonly used to help determine the etiology; however, the anion gap can be misleading in patients with low albumin and in the rare patients with an anion gap acidosis who are euvolemic. Winter's formula can be used to predict the Pco2 expected for the measured serum bicarbonate to determine if appropriate respiratory compensation is in place (Pco2 = 1.5 × [HCO3−] + 8 ± 2).

Increased Anion Gap

An elevated anion gap is synonymous with the presence of a metabolic acidosis and implies an overproduction of acids or a decrease in acid clearance by the kidney. The accumulation of acidic anions that are not measured by routine laboratory testing lowers the serum bicarbonate via buffering, thus generating an increased anion gap. An increased anion gap is associated with the following conditions:

• ketoacidosis
• diabetic
• alcoholic
• starvation
• renal failure
• lactic acidosis
• exogenous toxins metabolized to lactate—cyanide, carbon monoxide, ibuprofen, INH, iron, strychnine, toluene
• exogenous toxins metabolized to acids—aspirin, methanol, ethylene glycol, paraldehyde.

Nongap Acidosis

A metabolic acidosis with a normal anion gap is generated by the loss of bicarbonate with a reciprocal increase in chloride concentration, giving it its alternate name of hyperchloremic acidosis. The serum potassium concentration can be used to divide hyperchloremic acidosis into hypo- and hyperkalemic forms. Causes associated with hypokalemia include diarrhea, small bowel or pancreatic fistula, ureteral diversion, ileal loop, type 1 renal tubular acidosis (RTA), and the use of carbonic anhydrase inhibitors. Normal and hyperkalemic causes include type 4 RTA, early renal failure, hydronephrosis, tubulointerstitial renal disease, and hypoaldosteronism. Nongap acidosis may also result from rapid hydration with normal saline.

Calculation of the urinary anion gap can help identify the source of a nongap acidosis. The urinary anion gap is calculated by adding [Na+] and [K+] and subtracting [Cl−] and is used to determine urine ammonium excretion, which is difficult to measure directly. A positive value indicates that the renal ammonium production is impaired, pointing toward a renal source for the acidosis. A negative value is consistent with GI losses.

Physiology

The body buffers an acute metabolic acidosis by using intracellular and extracellular proteins, increasing H+ elimination by the kidney, and stimulating the respiratory drive. Respiratory compensation for a metabolic acidosis involves hyperventilation, and may take 12–24 hours to be fully effective. Under ordinary circumstances, a Pco2 of 10 mm Hg is the lower limit of compensation, with Pco2 falling by 1.0–1.3 for every 1 mEq/L decrease in [HCO3−].

Treatment

Treatment of metabolic acidosis requires treatment of the underlying cause. In many cases, reversing the underlying causes (e.g., DKA) and replacing volume will allow for the metabolism of organic acids back to bicarbonate or for the kidneys to regenerate bicarbonate. Maintaining adequate tissue perfusion and oxygenation is essential to avoid worsening the acidosis. The use of alkalinizing agents is controversial, as multiple studies have failed to demonstrate benefit from sodium bicarbonate administration and it could theoretically impair oxygen unloading in the tissues as well as result in increased CO2 formation, thereby worsening the acidosis. In severe cases (dysrhythmias, catecholamine insensitivity, hemodynamic instability), sodium bicarbonate may be used to raise the pH to 7.1 at a dose of 0.5 mEq/L/kg. Disposition depends on the severity of the underlying disorder, although nongap acidosis is rarely life threatening.

Metabolic Alkalosis

Essentials of Diagnosis

• Commonly results from vomiting or volume depletion secondary to diuretics
• Evaluate urine chloride concentration to help guide therapy

General Considerations

Metabolic alkalosis is defined as a primary elevation of serum [HCO3−] above 28 mEq/L with an elevation in pH above 7.44. A primary metabolic alkalosis results from the loss of acid or, more rarely, the gain of base. Gastric losses via vomiting or NG suctioning and diuretic use are common causes of metabolic alkalosis, with the resultant volume contraction maintaining the alkalosis. Various other medical conditions can result in a metabolic alkalosis, and determination of the urine chloride can help guide therapy (see Table 44–17).

Clinical Findings

Metabolic alkalosis produces hypokalemia, hypocalcemia, and hypomagnesemia. With severe alkalosis, signs of hypocalcemia may predominate. Decreased cerebral blood flow may result in lethargy and confusion, ultimately progressing to coma and seizures. A history of gastric losses or diuretic use may be obtained and signs of volume contraction on physical examination may be evident. Hypertension should raise the suspicion of primary aldosteronism. Patients with chronic hypercapnia may experience a metabolic alkalosis following correction of the hypercapnia.

Physiology

Respiratory compensation for a metabolic alkalosis consists of hypoventilation. For every increase of 1 mEq/L in the [HCO3−], Pco2 will rise by 0.7 mm Hg and pH increase by 0.015. Pco2 typically will not increase above 55 mm Hg because of the hypoxemia that ensues at that level of ventilation.

Treatment

Urine chloride concentration should be measured to guide initial therapy. Patients with a urine [Cl−] below 10 mEq/L are characterized as chloride responsive and should be treated with volume expansion using normal saline. Patients with a urine [Cl−] above 20 mEq/L may be chloride resistant; a urine [Cl−] above 40 mEq/L always indicates that sufficient volume expansion has occurred. Potassium replacement (up to 100–500 mEq) may be needed to correct the alkalosis in certain settings. Acetazolamide may be used in posthypercapnic metabolic alkalosis if volume status is normal. Disposition depends on the severity of the precipitating cause.

Mixed Acid–Base Disorders

Essentials of Diagnosis

• Up to three disorders can coexist
• Analyze the data in a stepwise fashion
• Calculate delta gaps and determine if appropriate compensation exists
• Metabolic acidosis and respiratory alkalosis commonly coexist

General Considerations

Respiratory acidosis and respiratory alkalosis can never coexist, but any other combination of processes is possible. Consider a mixed disorder whenever the degree of compensation is inadequate, or if an acid–base disorder causes no shift in pH (except in chronic respiratory alkalosis), or if the clinical picture is not consistent with a primary process.

Combined Metabolic Acidosis and Respiratory Acidosis

This is an ominous combination and is found in patients in cardiopulmonary arrest. Once a metabolic acidosis has been identified, determine if the Pco2 is appropriate; if it is higher than expected, a superimposed respiratory acidosis exists. In chronic respiratory acidosis, [HCO3−] should increase by 3.5 mEq/L for every increase of 10 mm Hg in Pco2. A smaller increase in [HCO3−] implies incomplete compensation or a superimposed metabolic acidosis.

Combined Metabolic Alkalosis and Respiratory Alkalosis

This mixed disorder is commonly encountered and may result from congestive heart failure, early sepsis, liver disease, or salicylate ingestion. It is identified by a respiratory compensation that is greater than expected for the degree of metabolic acidosis. In patients with chronic respiratory alkalosis, [HCO3−] should be decreased by 5 mEq/L for every 10 mm Hg decrease in Pco2. A greater decrease in [HCO3−] implies a superimposed metabolic acidosis.

Combined Metabolic Alkalosis and Respiratory Acidosis

This mixed disorder may occur in patients with chronic respiratory acidosis who develop a metabolic alkalosis from diuretic use. Appropriate compensation for a metabolic alkalosis is an increase in Pco2 of 0.7 mm Hg for each 1 mEq/L increase in [HCO3−]. A greater increase in Pco2 implies a superimposed respiratory acidosis. For patients with chronic respiratory acidosis, [HCO3−] should increase by 3.5 mEq/L for each increase in Pco2 of 10 mm Hg. Greater increases in [HCO3−] imply a superimposed metabolic alkalosis.

Combined Metabolic Alkalosis and Respiratory Alkalosis

This mixed disorder may result in patients with hepatic failure who are taking diuretics and in patients who require mechanical ventilation and are taking diuretics or undergoing NG suctioning. An increase in Pco2 of less than 0.7 mm Hg for each 1 mEq/L increase in [HCO3−] implies a superimposed respiratory alkalosis. In chronic respiratory alkalosis, [HCO3−] should be decreased by 5 mEq/L for every 10 mm Hg decrease in Pco2, with smaller decreases indicating a superimposed metabolic alkalosis.

Use of Delta Gaps to Identify Mixed Disorders

The use of the delta anion gap and delta bicarbonate can help identify mixed acid–base disorders that would not otherwise be readily apparent, including those with a normal pH. The delta anion gap is derived by subtracting 10 from the calculated anion gap. The delta bicarbonate is derived by subtracting the measured [HCO3−] from 24. For most commonly encountered anion gap acidoses, there will be a 1:1 relationship between the delta anion gap and the delta bicarbonate. When the delta bicarbonate exceeds the delta anion gap, a mixed anion gap and nongap acidosis is likely. When the delta bicarbonate is below the delta anion gap, a mixed anion gap acidosis with a metabolic alkalosis is likely (see Table 44–18).

Osmolality

Serum osmolality can be estimated using the following formula:

Osmolality is expressed in mOsm/L, sodium concentration is expressed in mEq/L, and glucose, BUN, and ethanol are expressed in mg/dL. A normal serum osmolal gap (measured osmolality minus calculated) is less than 10 mOsm/L. A widened osmolal gap may be seen in any condition that increases the amount of unmeasured osmoles in the blood, such as methanol or ethylene glycol ingestion or in DKA.

Electrolyte Replacement

In treating hyponatremia and hypernatremia, many different formulas that are available to help the clinician estimate total free water deficit or absolute sodium excess or deficiency. However, the use of the Adrogue–Madias equation offers a simple and reliable method for estimating the effect of infusion of 1 L of infusate on serum sodium.

Total body water may be estimated by multiplying the patient's weight by the appropriate value in Table 44–19 to obtain a value in liters. Sodium concentrations of common infusate solutions are provided in Table 44–20.

For example, in a 70-kg adult male who is symptomatically hyponatremic with a serum sodium of 120 mEq/L and who is clinically euvolemic, it may be desirable to increase the serum sodium by 2 mEq/L over 2 hours using 3% NaCl. In this case, 1 L of infusate would be expected to have the following effect on serum sodium:

Thus, 1 L should raise the patient's serum sodium by approximately 9 mEq/L. Giving the patient 222 mL total, or 111 mL/h for 2 hours, should result in an increase in the patient's serum sodium of 2 mEq/L.

Henderson–Hasselbalch Equation

Internal consistency of the acid–base data acquired from a blood gas can be ascertained by using the Henderson–Hasselbalch equation. For any given set of values, the following equation should be true:

Alternatively, the Henderson equation can be used to estimate [H+] directly and does not require the use of logarithms:

Over normal values of pH, [H+] can be estimated by starting at a [H+] of 40 nmol/L for a pH of 7.40, and adjusting the [H+] by 10 for every change in pH of 0.1. Other systems of describing physiologic acid–base balance, such as the standard base error and Stewart method, have been described and are more consistent with the known physical chemistry. However, for most clinical purposes the Henderson–Hasselbalch method is sufficient.