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Key Points
1. Water is the major component of all fluid compartments 8. Glucose is a crucial fuel source, and insulin facilitates
within the body and represents approximately 60% of glucose movement into cells in a process that also
body weight. requires potassium and phosphate.
2. Sodium is the most abundant positive ion of the 9. Diabetes affects multiple organ systems, and the
extracellular fluid (ECF) compartment and is crucial in perioperative effect of diabetes can be profound.
determining the extracellular and intracellular osmolality. 10. The most common causes of metabolic alkalosis are
3. Potassium is the most abundant positive ion in the antacid therapy, incidental administration of citrate with
intracellular fluid and plays an important role in the blood products, sodium bicarbonate administration,
membrane potential of cells. gastric drainage, and renal bicarbonate retention.
4. Calcium is the key component that mediates muscle 11. Metabolic acidosis is commonly caused by low cardiac
contraction; exocrine, endocrine, and neurocrine output and end-stage liver disease.
secretion; cell growth; and the transport and secretion 12. Transfusion of blood products improves tissue
of fluids and electrolytes. oxygenation and decreases bleeding, but it also
5. Magnesium is essential for many biochemical reactions; increases the risk of transmission of infectious diseases,
its pharmacologic properties have only more recently transfusion reactions, immunosuppression, and
been appreciated. alloimmunization.
6. Phosphate stores and releases energy through high- 13. Anesthetics may blunt the normal physiologic responses
energy phosphate bonds and is integral to the structure to hypovolemia and the stress response.
of proteins, lipids, and bone. 14. Shock is dysfunction of intracellular processes caused by
7. Chloride is the predominant anion in the ECF. the lack of energy.
1705
IV 1706 Anesthesia Management
Table 54-1 Electrolyte Composition in Body Fluids (Normal) at term, requirements are 2 to 3 mEq/kg/day (see Chapters 82
and 84).3 Neonatal stool losses are about 1mEq/kg/day, and the
Interstitial Fluid Intracellular
growth process uses 0.5mEq/kg/day. Adult requirements decrease
Electrolyte Plasma (mEq/L) (mEq/L) Fluid (mEq/L)
to about 1.5mEq/kg/day. Urinary sodium excretion represents
Na+ 142 145 10 most of the sodium loss and approximately equals the daily intake
K+
4 4 159
of sodium. Extrarenal sodium loss by profuse sweating, burns,
severe vomiting, or diarrhea is important.
Normally, 10mL of urine can initially be formed for each
2+
Mg 2 2 40
Ca 2+
5 3 1 1mOsm of solute excreted by the kidney. Normal kidneys respond
to a free water challenge with diuresis and to a sodium load with
Cl 103 117 10 natriuresis; if there is decreased sodium intake or volume deple-
HCO3
25 27 7 tion, the kidney responds with antinatriuresis and antidiuresis
(e.g., a patient undergoing surgery may excrete only 1.2 to
Adapted from Campbell I: Physiology of fluid balance. Anaesth Intensive Care Med
7:462-465 2006. 1.6mOsm/mL of solute). In various pathophysiologic processes,
abnormally high or low urinary sodium excretion can occur.
Many of the factors that control tubular sodium reabsorp-
of sodium, chloride, and bicarbonate. Permeability to ions and tion are affected during the perioperative period, including hemo-
proteins varies with each organ, with the brain having the lowest dynamic and physical factors (e.g., increased intra-abdominal
and the liver having the highest permeability. pressure during laparoscopic procedures), hormonal factors, and
Control of body water and its composition is multifactorial renal sympathetic nerve activity. The balance of Starling forces
and involves many factors, including atrial natriuretic peptide (hydrostatic versus osmotic) is responsible for sodium and water
(ANP), vasopressin (i.e., antidiuretic hormone [ADH]), aldoster- transport across peritubular capillary walls. The net pressure in
one (e.g., renin, angiotensin), parathyroid hormone, calcitonin, the peritubular capillaries is about 10mmHg in favor of uptake
prostaglandins, dopaminergic receptors, -adrenergic receptors, of reabsorbed fluid. Volume expansion with isotonic saline
the thirst mechanism, and intrinsic renal properties. Water balance decreases plasma protein concentration and reduces colloidal
describes the difference between water intake and water loss. The osmotic pressure (COP) in peritubular capillaries.
kidneys are the major regulators of water output. The renin-angiotensin system (RAS) is involved in control
Approximately 60% of the daily water loss is excreted in of arterial blood pressure and blood volume along with the sym-
the urine. At high ambient temperatures or with significant exer- pathetic nervous system, the kinin-kallikrein system, and arginine
cise, the amount of water lost by sweating increases and may vasopressin. The RAS plays a role in sodium homeostasis and
reflect most of the total daily water loss (Table 54-2). Heavy exer- renal function, particularly under stress conditions. The RAS may
cise can increase the loss of water through sweating 50 times the be initiated by decreases in blood pressure in the renal artery, by
normal rate. Increased ventilation amplifies the insensible loss of decreases in sodium delivery to the macula densa, or by sympa-
water through the respiratory tract. Under these conditions, renal thetic nervous system activation. In response, renin is synthesized
water loss decreases to compensate for the increased sweating and from its precursor, prorenin, and secreted by the juxtaglomerular
insensible water losses.1 cells of the kidney. Renin, an aspartyl-protease (similar to pepsin
and cathepsin), cleaves its substrate, angiotensinogen, which is an
2-globulin, to generate the decapeptide angiotensin I. Although
renin is mostly produced by the kidney, renin isoenzymes have
Sodium Physiology been found in many tissues, including brain, adrenals, vascular
beds, uterus, and placenta.4 The gene for human renin has been
Sodium is the most abundant positive ion of the ECF and is cloned. Angiotensinogen levels are increased after nephrectomy,
crucial in determining the extracellular and intracellular osmolal- by estrogens, by thyroid hormones, by glucocorticoids, and during
ity. Serum osmolality is tightly regulated between 275 and angiotensin Iconverting enzyme inhibition.5,6
290mOsm/kg, primarily through the influence of ADH, and is Angiotensin I is rapidly converted to the octapeptide angi-
estimated by the following equation: otensin II by angiotensin Iconverting enzyme or by an endopepti-
Serum osmolality = (2 Na ) + ( glucose 18) + (urea 2.8)
Table 54-2 Daily Loss of Water
Osmoreceptors in the hypothalamus can detect changes of
1%. Most patients with hyponatremia have urine osmolality of Normal Activity Normal Activity Prolonged
Source of and Temperature High Temperature Exercise
more than 200mOsm/kg, reflecting impairment in water excre-
Loss (mL) (mL) (mL)
tion.2 With regard to sodium physiology, the ratio of sodium
between plasma and interstitial fluid is roughly 5:1 at equilib- Urine 1400 1200 500
rium. The distribution equilibrium is usually complete within 15 Sweat 100 1400 5000
to 20 minutes. Extracellular sodium balance is determined by
sodium intake relative to sodium excretion. Most humans Feces 100 100 100
consume far more salt than they need. In normal, healthy indi- Insensible 700 600 1000
viduals, the kidneys main function in sodium balance is excretion losses
of excess sodium.
Total 2300 3300 6600
Sodium requirements vary with age. For infants born
before 32 weeks gestation, requirements are 3mEq/kg/day, and From Rhoades RA, Tanner GA: Medical Physiology. Boston, Little, Brown, 1995.
Intravascular Fluid and Electrolyte Physiology 1707 54
dase. The pulmonary circulation seems to be the major site of Table 54-4 Causes of Hyponatremia as Related to Intravascular
angiotensin-converting enzyme activity, although angiotensin- Volume Status
converting enzyme also is found in the vascular endothelium of
Hypovolemic Hypervolemic Euvolemic
the heart, kidney, adrenal cortex, testes, and brain.7
Angiotensin II is a potent vasopressor that stimulates Hemorrhage Congestive heart failure SIADH
aldosterone secretion through the adrenal cortex. Angiotensin II Burn wound edema Nephrotic syndrome Pseudohyponatremia
has a vagal inhibitory effect and causes ganglionic stimulation.8-10 Peritonitis Cirrhosis syndrome
Angiotensin II partially suppresses renin secretion by a direct Cerebral salt-wasting TURP syndrome
secreted intermittently at an abnormally low threshold or con- Table 54-5 Major Causes of Hyponatremia
tinuously despite low osmolality. The presence of hyponatremia
Mechanism Clinical Syndromes
plus a urine osmolality higher than maximal dilution confirms
the diagnosis. In patients with SIADH, the urinary sodium con- Pseudohyponatremia (normal Hyperlipidemia, hyperproteinemia
centration usually exceeds 30mEq/L, the fractional excretion of osmolality)
sodium is greater than 1%, and the serum uric acid is reduced. Dilutional hyponatremia due to Hyperglycemia, mannitol administration
Patients with SIADH exhibit a characteristic response to water serum hyperosmolality
restriction; a 2- to 3-kg weight loss is accompanied by correction
of hyponatremia and cessation of salt wasting over 2 to 3 days. True hyponatremia with normal -globulins, lithium, THAM
effective osmolality
This is another example of true hypotonic hyponatremia.
Hyponatremia also occurs in mixed disorders, in which True hyponatremia with edema Congestive heart failure, nephrotic
nonosmotic ADH release and reductions in the rate of urinary (sodium excess)low effective syndrome, cirrhosis of the liver,
sodium excretion blunt urinary diluting capacity. This can occur osmolality idiopathic edema, hypoalbuminemia
in advanced volume contraction, intractable heart failure, and (e.g., due to malnutrition)
advanced hepatic cirrhosis with ascites. True hyponatremia (sodium Renal wasting (diuretics, renal tubular
It is crucial for the anesthesiologist to recognize the signs depletion)low effective acidosis, cerebral salt-wasting
and symptoms associated with hyponatremia, particularly for osmolality syndrome); extrarenal wasting
TURP syndrome managed with regional anesthesia. An awake (vomiting, diarrhea, ostomy losses)
patient permits detection of the signs of hyponatremia, including Hyponatremia with normal or SIADH, water intoxication due to
nausea, vomiting, visual disturbances, depressed level of con- expanded effective arterial primary polydipsia, water overload
sciousness, agitation, confusion, coma, seizures, muscle cramps, volume due to advanced renal failure or
weakness, myoclonus, coma, and death. Cerebral edema occurs at vascular or inflammatory renal
or below a serum level of 123mEq/L, and cardiac symptoms disease
occur at 100 mEq/L. Hyponatremia associated with increased
Reduced sodium delivery to Starvation, myxedema (?)
intravascular volume can result in pulmonary edema, hyperten- diluting segment
sion, and heart failure.19
Initially, stopping the infusion of hypotonic glycine solu- SIADH, syndrome of inappropriate secretion of antidiuretic hormone;
THAM, tris(hydroxymethyl)aminomethane.
tion can resolve or at least improve the progression of Adapted from Oh M, Carrol H: Disorders of sodium metabolism: Hypernatremia and
hyponatremia. Because TURP syndrome is a case of water over- hyponatremia. Crit Care Med 20:94, 1992; and from Andreoli TE: Disorders of fluid
load, the treatment should include water restriction. A loop diu- volume, electrolyte, and acid-base balance. In Wyngaarden JB, Smith LH Jr (eds):
retic may be added to facilitate free water excretion. Hypertonic Cecil Textbook of Medicine, 17th ed. Philadelphia, WB Saunders, 1985, p 525.
saline should be used only in cases of severe hyponatremia with
neurologic symptoms.20
In any patient whose hyponatremia warrants correction,
the dose of sodium required to correct a deficit may be calculated antagonists and the administration of urea as an osmotic diuretic
using the following formula: are under investigation.
Rapid treatment of hyponatremia can lead to cerebral
( ( ))
Dose [mEq ] = weight [ kg ] 140 Na + mEq L 0.6 edema or central pontine myelinolysis. Management of
hyponatremia involves elimination of the underlying condition
The optimal rate of correction seems to be 0.6 to 1mmol/L/hr when possible (e.g., stop TURP syndrome as soon as possible).
until the sodium concentration is 125mEq/L; correction then The use of normal saline (308mOsm/L) alone may worsen the
proceeds at a slower rate. One half the deficit can be administered hyponatremia, depending on the patients serum and urine osmo-
over the first 8 hours, and the next half can be administered over lality.23 Severe coma or seizures can be managed with one or more
1 to 3 days if symptoms remit. The appropriate treatment of approaches, including 3% hypertonic saline (513mEq/L), fluid
hyponatremia, particularly in patients with neurologic restriction, or furosemide.24 The most likely cause of postopera-
symptoms, is, however, an area of controversy. Sodium concentra- tive hyponatremia is SIADH (Table 54-5). SIADH and cerebral
tion should be monitored every 1 to 2 hours during rapid salt-wasting syndrome can best be differentiated by determina-
correction. tion of total-body water by clinical measurements, including skin
Menstruant female patients are at greater risk for develop- turgor, body weight, central venous pressure (CVP), and overall
ing significant neurologic sequelae after hyponatremia. Ayus and vital signs.
colleagues21 found that despite equal incidence of postoperative
hyponatremia among men and women, 97% of patients with per-
manent brain damage were women, and 75% of those were of Hypernatremia
reproductive age. The mechanism of this gender difference is
unknown; however, a potential explanation involves alterations in Hypernatremia is defined as an increase in extracellular sodium
the brains adaptive processes to hyponatremia. Estrogens seem concentration, and may be accompanied by the presence of low,
to alter the function of Na+/K+-ATPase in the rat brain, which normal, or high total-body sodium content. The major causes of
could alter the brains compensatory mechanisms for hypernatremia are excessive loss of water, inadequate intake of
hyponatremia.22 Several agents that interfere with urine concen- water, a lack of ADH, or excessive intake of sodium (e.g., with
tration at the collecting duct, including lithium and demeclocy- solutions containing a high sodium concentration, such as sodium
cline, have been used to manage chronic hyponatremia. ADH bicarbonate or hypertonic saline).
Intravascular Fluid and Electrolyte Physiology 1709 54
Diabetes insipidus may result from a deficiency of ADH Table 54-7 Major Causes of Hypernatremia
(vasopressin) or inability of the kidney to produce a hypertonic
Mechanism Clinical Syndrome(s)
medullary interstitium. Diabetes insipidus is characterized by
production of a large volume of dilute urine. Deficiency of vaso- Impaired thirst Stupor/coma, essential hypernatremia
pressin is known as central diabetes insipidus and is an endocrine
Solute (osmotic) diuresis Diabetic ketoacidosis, hyperglycemic
disorder. Vasopressin deficiency is seen after pituitary surgery, nonketotic coma, mannitol administration
basal skull fracture, and severe head injury. Conversely, nephro-
genic diabetes insipidus results if the kidney cannot produce a Excessive water losses
conductance leads to transmembrane potential being closer to the No studies show increased morbidity or mortality for
transmembrane value of potassium (90mV). Alterations in patients undergoing anesthesia with a potassium level of at least
extracellular potassium concentration alter the resting membrane 2.6mEq/L. Anesthesiologists commonly administer supplemen-
potential, which may cause the cell to be unresponsive or over- tal potassium chloride, but studies show that in many instances
responsive to sodium shifts into the cell. High or low potassium therapy is ineffective, with most of the supplemental potassium
levels can result in potentially lethal problems in excitatory tissue, being excreted in the urine despite continued hypokalemia.31,32 If
particularly cardiac tissue. perioperative therapy is indicated, intravenous potassium chlo-
Multiple factors regulate the normal maintenance of the ride should be used. Because the rate of administration of potas-
transmembrane potassium gradient. The most important trans- sium must be adjusted for the rate of distribution through the
cellular enzyme involved in potassium regulation is Na+/K+- extracellular space before entry into the intracellular space, the
ATPase, which maintains the transcellular gradient. 2-Adrenergic rate of potassium administration is typically limited to approxi-
drugs increase the activity of Na+/K+-ATPase by binding to cell mately 0.5mEq/kg/hr. The typical replacement rate is 10 to
surface receptors, linking potassium transport to the sympathetic 20mEq/hr for a normal adult with constant monitoring of the
nervous system. Insulin causes more sodium to enter the cell electrocardiogram.33,34 Clinical anesthesiologists should be aware
through an Na+/H+-antiporter, which decreases intracellular that safe administration of potassium is enhanced by the use of
proton concentration. To maintain electric neutrality, any increase continuous electrocardiogram monitoring, bedside potassium
in sodium must occur via exchange for potassium, decreasing measurement, and delivery with an infusion pump (Table 54-8).
extracellular potassium. Shock can have an adverse impact on the
activity of Na+/K+-ATPase by limiting the amount of adenosine
triphosphate (ATP) available for ion transport because of the shift Hyperkalemia
to anaerobic metabolism.27 Potassium transport is affected by pH.
The body uses potassium to decrease excess extracellular hydro- Hyperkalemia (>5.5mEq/L) can occur in various disease states,
gen ions by moving potassium out of cells and hydrogen ions into in response to drugs that diminish renal potassium excretion
cells. Acidemia potentiates hyperkalemia by moving potassium (Table 54-9), or after sudden transcellular shifts of potassium
out of cells. from the intracellular fluid to the ECF. Potentially lethal hyperka-
Potassium requirements vary with age and growth. A lemia during anesthesia may occur with reperfusion of a large
typical term infant requires 2 to 3 mEq/kg/day,28 whereas adults vascular bed after a period of ischemia (usually >4 hours).
use 1 to 1.5mEq/kg/day (see Chapters 82 and 84). Potassium Ischemia results in significant acidosis in the affected area, which
demands are related to metabolic rate (2mEq/100kcal). In this causes an outflow of intracellular potassium. When the area is
regard, the requirement increases dramatically during cell growth reperfused, the body receives a large bolus of potassium that
after establishment of nutrition in previously starved individuals. cannot be redistributed rapidly enough, resulting in potentially
An extremely high or low level of potassium is life-threatening. fatal hyperkalemia. Any condition or drug resulting in adrenal
inhibition or decreasing aldosterone levels can cause potassium
retention. Factitious (e.g., spurious) hyperkalemia also should be
Hypokalemia considered in the differential diagnosis and occurs in response to
lysis of the cellular components of blood.
Hypokalemia (<3.5mEq/L) may occur because of an absolute
deficiency or redistribution into the intracellular space. A reduc-
tion in serum potassium of 1mEq/L indicates a net loss of 100
Table 54-8 Major Causes of Hypokalemia
to 200mEq of potassium in a normal adult. Hypokalemia in the
range of 2 to 2.5mEq/L is likely to cause muscular weakness, Mechanism Clinical Syndromes
arrhythmias, and electrocardiographic abnormalities, including
sagging of the ST segment, depression of the T wave, and U wave Inadequate intake Anorexia nervosa, starvation, alcoholism,
elevation. These electrocardiographic changes do not correlate mineralocorticoid excess (primary and
secondary hyperaldosteronism)
with the severity of potassium depletion. Cardiac dysrhythmias
are more predictable, however, and most frequently involve atrial Excess renal loss Bartters syndrome; diuresis (diuretics with a
fibrillation and premature ventricular systoles. pre-late distal locus osmotic diuresis, chronic
The four most common causes of hypokalemia are reduced metabolic alkalosis); impermeant anion
intake, gastrointestinal losses, excessive renal losses of potassium antibiotics (carbenicillin, penicillin, nafcillin,
(e.g., with excess of mineralocorticoids or diuretics), and potas- ticarcillin); renal tubular acidosis;
hypomagnesemia; myelomonocytic leukemia
sium shifts from the ECF to the intracellular fluid (e.g., owing to
insulin administration). Such shifts can occur with acute alkalosis, Gastrointestinal losses Vomiting; diarrhea, particularly secretory
insulin therapy, stress-related catecholamine activity, and hypoka- diarrheas; villous adenoma
lemic periodic paralysis. Surgical stress may reduce the serum Shifts of extracellular 2-agonists, acute alkalosis, hypokalemic
potassium concentration by 0.5mEq/L. The administration of fluid to intracellular periodic paralysis, insulin therapy, vitamin B12
exogenous catecholamines, such as isoproterenol, terbutaline, fluid with altered therapy, lithium overdose
epinephrine, and ritodrine, also decreases potassium levels29,30; internal potassium
clinically, this includes pregnant patients receiving tocolytic balance
therapy or respiratory treatment with 2-agonists and critically ill Adapted from Andreoli TE: Disorders of fluid volume, electrolyte, and acid-base
patients requiring pharmacologic cardiovascular support (see balance. In Wyngaarden JB, Smith LH Jr (eds): Cecil Textbook of Medicine, 17th ed.
Chapters 69 and 92). Philadelphia, WB Saunders, 1985, p 532.
Intravascular Fluid and Electrolyte Physiology 1711 54
Table 54-9 Drugs Causing Hyperkalemia feces and urine. Circulating calcium exists in three forms: bound
to plasma proteins (primarily albumin) and not filtered by
Amiloride
glomerular capillaries (40% to 50%); ionized, physiologically
Angiotensin II antagonists
Angiotensin-converting enzyme inhibitors
active, filtered at the glomerular membrane, and maintained at a
Mannitol concentration of 2 to 2.5mEq/L (50%); and nonionized and
Pentamidine chelated with phosphate, sulfate, and citrate (10%). Because
Spironolactone changes in pH alter the fraction of calcium that is bound to
Succinylcholine albumin, the level of ionized calcium can change without altera-
roid hormone, which increases calcium reabsorption in the thick Table 54-11 Major Causes of Hypercalcemia
ascending limb and distal tubule, decreasing calcium excretion.
Mechanism Clinical Syndromes
Excision of the parathyroid glands eliminates parathyroid
hormone secretion, which can significantly disrupt calcium Increased Primary hyperparathyroidism (solitary or multiple
homeostasis. parathyroid adenoma, multiple endocrine neoplasia syndrome),
Calcitonin, produced in the thyroid gland, decreases renal hormone lithium therapy, familial hypocalciuric hypercalcemia
reabsorption of calcium acutely, but has little effect on long-term Vitamin D related Vitamin D intoxication; idiopathic hypercalcemia of
calcium homeostasis. Surgical removal of the thyroid gland elimi- infancy; increase in 1,25-dihydroxyvitamin D;
nates calcitonin without changing extracellular calcium ion sarcoidosis and other granulomatous diseases
concentration.
Associated with Hyperthyroidism, immobilization, thiazides, vitamin A
Bone acts as the bodys major reservoir of calcium. When high bone intoxication
the parathyroid gland releases parathyroid hormone in response turnover
to decreased calcium levels, bone reabsorption is favored, and
calcium is released. Vitamin D increases absorption of calcium Malignancy Solid tumors with metastases, solid tumors with
from the gastrointestinal tract, and its action is potentiated by related, humoral mediators of hypercalcemia, hematologic
including malignancies, severe secondary
parathyroid hormone.
associated with hyperparathyroidism (from chronic renal failure),
renal failure aluminum intoxication, milk-alkali syndrome
Hypercalcemia Adapted from Potts JT: Diseases of the parathyroid gland and other hyper- and
hypocalcemic disorders. In Isselbacher KJ, Braunwald E, Wilson JD, et al (eds):
Harrisons Principles of Internal Medicine, 13th ed. New York, McGraw-Hill, 1995, p
Hypercalcemia is associated with many disease processes and has 2151.
many signs and symptoms. Mild to moderate hypercalcemia (11
to 14mg/100mL) often has no symptoms, but when levels reach
15mg/100mL, clinical changes become more common. Hyper- greater than 1.5mL/kg/min (see Chapter 55). The most common
calcemia produces changes primarily in the central nervous cause of hypocalcemia (plasma concentration <4.5mEq/L) in
system (e.g., mental status changes), the gastrointestinal tract hospitalized patients is a low albumin level, such as in critically
(e.g., vomiting), the kidneys (e.g., polyuria, renal calculi, oliguric ill patients with severe sepsis, burns, or acute renal failure, and in
renal failure), and the heart (e.g., cardiac conduction distur- patients after extensive transfusions. Critically ill patients can
bances). Today, hypercalcemia is most commonly diagnosed in have low plasma albumin and low plasma calcium levels with
asymptomatic patients, whereas clinical features previously were normal ionized calcium levels. There is no reason to correct the
the earliest manifestations. Potential causes of hypercalcemia calcium deficiency, but overall nutrition should be improved. The
include thiazide diuretic therapy, malignancy (now known as major signs and symptoms of hypocalcemia include mental status
humoral hypercalcemia of malignancy), granulomatous disease changes, tetany, positive Chvostek and Trousseau signs, laryngo
(related to increased intestinal absorption of calcium induced by spasm, hypotension, and dysrhythmias. Electrocardiographic
elevated calcitriol levels), vitamin D intoxication, or parathyroid evaluation may show prolongation of the QT interval or heart
hormone adenoma. Additional causes of hypercalcemia include block in severe cases. Treatment, often prompted by hypotension,
lithium therapy, thyrotoxicosis, pheochromocytoma, immobiliza- involves intravenous infusion of 10% calcium chloride (1.36mEq/
tion, vitamin A intoxication, renal failure, and theophylline mL) or calcium gluconate (0.45mEq/mL). When equivalent
therapy. calcium doses are administered, both preparations are equally
Treatment of hypercalcemia essentially involves diuresis efficacious in restoring the calcium level to normal (Table 54-12).
and administration of normal saline to dilute plasma calcium. In this regard, calcium gluconate is especially advantageous in
These primary treatments also are useful because sodium inhibits peripheral venous administration because extravasated calcium
the renal reabsorption of calcium. Additional therapies include chloride solution can result in severe tissue destruction.
bisphosphonates (pamidronate is the most commonly used), When hypocalcemia is caused by large-volume infusion of
calcitonin, ambulation, hemodialysis, and treatment of the under- isotonic saline (as seen during resuscitation in shock), it may be
lying condition. Certain conditions, including numerous cancer- accompanied by hypomagnesemia. Hypomagnesemia may impair
related hypercalcemias, can be treated with calcium-lowering the actions of vitamin D and delay correction of postresuscitation
agents, such as mithramycin and glucocorticoids. The anesthetic hypocalcemia. The magnesium level should be checked and cor-
management of a patient with hypercalcemia should involve rected if necessary. In this regard, fluid resuscitation involving
avoidance of thiazide diuretics and maintenance of hydration and certain colloids can contribute to a hypocalcemic state.37
urine output with sodium-containing fluids. Monitoring the
patient by means of electrocardiograms is useful to detect cardiac
conduction abnormalities with shortened PR or QT interval,
with or without widening of the QRS complex. Patients who have Magnesium Physiology
muscle weakness should receive decreased doses of nondepolar-
izing muscle relaxants (Table 54-11). Magnesium sulfate has been used for many years on an empirical
basis to control convulsions in patients with preeclamptic toxemia.
Magnesium ions are essential for many biochemical reactions,
Hypocalcemia and a deficiency may produce clinically important consequences.
Many of the pharmacologic properties have only more recently
In the operating room, ionized hypocalcemia is most commonly been appreciated. Magnesium is excreted through the gastroin-
caused by acute hyperventilation or the infusion of citrated blood testinal tract and kidneys.
Intravascular Fluid and Electrolyte Physiology 1713 54
Table 54-12 Major Causes of Hypocalcemia Excluding Neonatal Conditions of 1 to 2g over approximately 5 minutes intravenously with close
monitoring of blood pressure and heart rate. Arterial pressure,
Mechanism Clinical Syndromes
deep tendon reflexes, and magnesium concentration may aid the
Parathyroid hormone absent Hereditary hypoparathyroidism, acquired clinical anesthesiologist when overtreatment is suspected. In
hypoparathyroidism, hypomagnesemia asymptomatic patients with mild hypomagnesemia, oral replace-
Parathyroid hormone Lack of active vitamin D (decrease in intake
ment is preferred. Beyond the theoretical risks of magnesium
ineffective or lack of sunlight), defective metabolism deficiency and neuromuscular blockade, the clinical importance
from anticonvulsant therapy, vitamin D of hypomagnesemia is related to the conditions and pathophysi-
Hypomagnesemia
Table 54-13 Major Causes of Hypomagnesemia
With an absence of magnesium in the diet, the kidneys are able
to decrease excretion significantly; however, hypomagnesemia is Mechanism Clinical Syndromes
common in hospitalized patients, especially patients in critical Primary nutritional Inadequate intake, total parenteral nutrition,
care areas, and it manifests with signs and symptoms similar to disturbances refeeding syndrome
hypocalcemia. Slight hypomagnesemia occurs in athletes, in
Gastrointestinal disorders Specific absorptive defects, malabsorption
hypermetabolic states such as pregnancy, and during cold accli-
syndromes, prolonged diarrhea, prolonged
matization. Magnesium stores can become depleted in patients
nasogastric suction, pancreatitis
undergoing prolonged diuretic therapy or patients with chronic
diarrhea. Chronic alchohol ingestion leads to significant loss of Endocrine disorders Hyperparathyroidism, hypoparathyroidism,
magnesium, and most hospitalized alcoholics have low magne- hyperthyroidism, primary
sium levels. Magnesium deficiency alone or in combination with hyperaldosteronism, Bartters syndrome,
diabetic or alcoholic ketoacidosis,
diuretic-induced hypokalemia and digitalis-induced arrhythmia
administration of epinephrine, SIADH,
responds to magnesium therapy.38
hungry bone syndrome after
Anesthetizing patients with magnesium deficiency is likely parathyroidectomy
to increase the risk of perioperative arrhythmias. Respiratory
muscle power is impaired by hypomagnesemia, which may have Chronic alcoholism, Ethanol ingestion; idiopathic; after renal
important clinical consequences for anesthesia and critical care. alcoholic withdrawal, transplantation; drugs (cisplatin,
increased renal excretion aminoglycoside, amphotericin B, diuretics,
Additional manifestations include central nervous system irrita-
pentamidine, theophylline); recovery phase
bility with seizures and hyperreflexia (e.g., Chvostek sign) and of acute tubular necrosis; colony-
skeletal muscle spasm (e.g., Trousseau sign). Treatment in a 70-kg stimulating factor therapy
adult with normal renal function in whom intravenous therapy
is warranted includes magnesium sulfate 1 to 2g (8 to 16mEq) SIADH, syndrome of inappropriate secretion of antidiuretic hormone.
Adapted from Potts JT: Diseases of the parathyroid gland and other hyper- and
over 15 minutes followed by 1g/hr until serial serum magnesium hypocalcemic disorders. In Isselbacher KJ, Braunwald E, Wilson JD, et al (eds):
levels indicate the deficiency has been corrected.39 For acute Harrisons Principles of Internal Medicine, 13th ed. New York, McGraw-Hill, 1995,
arrhythmias, magnesium sulfate can be administrated in a dose p 2188.
IV 1714 Anesthesia Management
cant presynaptic neuromuscular blockade and enhance the action The deleterious effects of magnesium deficiency are well
of the nondepolarizing muscle relaxants.40 It can precipitate recognized, and most critical care units monitor magnesium
severe muscle weakness in patients with Eaton-Lambert syn- levels. In coronary care units, several studies have shown that the
drome, patients with myasthenia gravis, or patients pretreated infusion of magnesium sulfate can reduce the incidence and
with a small dose of a defasciculating agent.40 Magnesium pro- severity of cardiac arrhythmias associated with myocardial infarc
longs the action of depolarizing neuromuscular blocker drugs tion. Numerous reports in the literature describe the bronchodi-
(e.g., succinylcholine); administration before the use of succinyl- lator effect of magnesium and its successful use in the management
choline prevents the release of potassium provoked by the neu- of asthma. Magnesium may decrease the incidence of adrener
romuscular blocking drug (see Chapter 29). gically mediated arrhythmias without interfering with the bron-
In the cardiovascular system, magnesium produces vasodi- chodilating action of -stimulants and contribute to smooth
lation by direct action on blood vessels and by interfering with a muscle relaxation of bronchioles.40
wide range of vasoconstrictor substances. It also reduces periph- Magnesium has several important pharmacologic actions.
eral vascular tone by sympathetic blockade and inhibition of cat- Its route of elimination is renal, and any patient who is oliguric
echolamine release.40 In the isolated heart, increased concentrations or in a reduced urine output state requires downward dosing
of extracellular magnesium ion markedly depress contractile adjustment of magnesium therapy. Magnesium should be regarded
force. Decreased myocardial performance has been shown after a as a cardiovascular drug, first and foremost, with calcium antago-
bolus of 2.5g of magnesium sulfate. Severe myocardial depres- nistic and antiadrenergic properties that may be accompanied by
sion can occur with combinations of magnesium and diltiazem. minimal myocardial depression.40
In the isolated heart, magnesium produces bradycardia, but in an
intact subject, the inhibition of vagal acetylcholine release pro-
duced by magnesium overrides the intrinsic slowing, and a mild Phosphate Physiology
tachycardia occurs. Magnesium is effective in treating various
arrhythmias, including ventricular arrhythmias, torsades de Phosphate is the most abundant intracellular anion, and is essen-
pointes, arrhythmias associated with epinephrine administration, tial for membrane structure, cellular energy, and cell transport.
and digitalis-associated arrhythmias. It also is efficacious in Specifically, phosphate is required to produce ATP, DNA, RNA,
certain arrhythmias induced by hypokalemia, alcoholism, and and 2,3-diphosphoglycerate, which facilitates oxygen release from
myocardial infarction, and may offer partial protection against hemoglobin. About 1g of phosphorus is ingested daily. Intake
bupivacaine-induced arrhythmias. generally exceeds metabolic requirements. Approximately 70%
In the respiratory system, magnesium has no effect on (700mg) is absorbed primarily from the small intestine, with the
central respiratory drive, and its only respiratory depressant effect rest (300mg) eliminated in the feces. In addition to 1,25-dihy-
is caused by the neuromuscular blockade that it produces. It is an droxyvitamin D3 (vitamin D), parathyroid hormone facilitates
effective bronchodilator and has been used successfully in severe absorption of phosphate from the gut lumen. The gut secretes
acute asthma, although no study to date has shown benefit in phosphate into the lumen and then reabsorbs it, unless it is bound
chronic asthma. there by calcium or antacids or is lost by diarrhea or drainage
In obstetric practice, magnesium, at supraphysiologic con- through ostomies or fistulas. Under normal dietary conditions,
centrations, is a powerful tocolytic and has been used for many absorption of phosphate occurs through paracellular diffusive
years in the management of premature labor. Magnesium also is pathways with little regulation. When luminal phosphate concen-
used in obstetrics to prevent patients with preeclampsia from trations are low, an active sodium-dependent transport mecha-
developing seizures. Animal studies have shown that magnesium nism is activated, and additional phosphate is absorbed.41 When
suppresses electroencephalographic spike activity (see Chapter dietary intake is normal, phosphate absorption is essentially an
69). Therapeutic magnesium levels are 5 to 7mg/dL when admin- unregulated process. Cations such as calcium, magnesium, and
istered for preeclampsia. When levels exceed 15 to 20mg/dL, aluminum decrease phosphate absorption, however, by directly
respiratory depression can become profound. In the kidney, mag- binding with phosphate in the gut lumen. This is useful clinically
nesium is a renal vasodilator and a diuretic. in renal failure to limit the amount of phosphate reabsorbed by
Symptoms and electrocardiographic changes of hypermag- the gut. Because of the unregulated nature of phosphate absorp-
nesemia correspond to serum levels. Depressed cardiac conduc- tion in the gut, the kidneys become the primary organ of excre-
tion, widened QRS complexes, prolonged PR intervals, and tion of excess phosphate. The kidneys normally excrete 700mg/day
nausea appear with levels of 5 to 10mg/dL. Sedation, hypoventila- by filtering 6g and reabsorbing 5.3g. Urinary phosphate elimina-
tion, decreased deep tendon reflexes, and muscle weakness appear tion approximately equals intestinal absorption.
with levels of 20 to 34mg/dL, with hypotension, bradycardia, and As mentioned, phosphate stores and releases energy
diffuse vasodilation occurring at levels of 24 to 48mg/dL. Are- through high-energy phosphate bonds and is integral to the
flexia, coma, and respiratory paralysis occur at 48 to 72mg/dL. structure of proteins, lipids, and bone (hydroxyapatite). Bone
For these reasons, all patients being treated with magnesium functions as the primary reservoir of phosphate and calcium in
therapy are clinically observed for magnesium intoxication. the body. When the body requires extra calcium, bone is broken
Elimination of magnesium involves fluid loading followed down to release calcium for the bodys use. In addition to calcium,
by or with concomitant diuresis. Definitive therapy involves dialy- significant amounts of phosphate also are liberated. This balance
sis. Temporary reversal of the effects of magnesium can be is controlled by the regulatory processes discussed in the previous
managed with calcium therapy. Because hypermagnesemia poten- section.
tiates the effects of depolarizing and nondepolarizing muscle Factors favoring cellular uptake include ingestion of glucose
relaxants, these agents must be carefully titrated in conjunction or fructose, alkalosis, insulin level, -adrenergic stimulation, and
with appropriate assessment of neuromuscular blockade. anabolism. Phosphate occurs in organic or inorganic forms. Most
Intravascular Fluid and Electrolyte Physiology 1715 54
intracellular phosphate is organic. Plasma contains lipid phos- Table 54-14 Major Causes of Hyperphosphatemia
phates, organic ester phosphates, and inorganic phosphates,
Mechanism Clinical Syndromes
including divalent (HPO42) and monovalent (H2PO4) phos-
phate. At physiologic pH, 80% of the inorganic phosphate is diva- Binding to serum Including plasma cell dyscrasias
lent. Normally, plasma inorganic phosphate is maintained at 3 to proteins
4.5mg/100mL in adults and 4 to 5mg/100mL in children. Par- Decreased renal Renal insufficiency, hypoparathyroidism,
athyroid hormone inhibits proximal tubular inorganic phosphate excretion pseudohypoparathyroidism types I and II, tumoral
reabsorption and increases inorganic phosphate excretion. calcinosis, pseudoxanthoma elasticum, infantile
Adapted from Potts JT: Diseases of the parathyroid gland and other hyper- and
Severe hyperphosphatemia occurs after tissue damage or cell hypocalcemic disorders. In Isselbacher KJ, Braunwald E, Wilson JD, et al (eds):
death. Moderate to severe hyperphosphatemia may be caused by Harrisons Principles of Internal Medicine, 13th ed. New York, McGraw-Hill, 1995, p
an impaired ability to excrete phosphorus because of renal failure. 2186.
As renal failure worsens, and the glomerular filtration rate declines
to less than 25mL/min, hyperphosphatemia may develop. Other care unit), malnutrition, sepsis, trauma, diuretic or steroid therapy,
causes include iatrogenic, hypothermia, massive liver failure, ketoacidosis, osmotic diuresis, acidosis, and catabolic states.
and certain hematologic malignancies associated with high cell Depressed intake or absorption and increased urinary losses are
turnover. The increased cell turnover can be part of the malig- common causes. Starvation for 48 hours and poor nutritional
nancy or may result from cell destruction when chemotherapy is status predispose to hypophosphatemia. In individuals with
instituted. chronic alcoholism, reduction of the phosphorus content of
Hypoparathyroidism can cause hyperphosphatemia in the skeletal muscle occurs as a result of renal phosphate loss. The
presence of normal renal function. Rapid increases in serum hypophosphatemic syndrome includes phosphate trapping, rhab-
phosphate can lead to development of severe hypocalcemia. domyolysis, cardiomyopathy, respiratory insufficiency from pro-
Hypocalcemia results from decreased calcitriol production, which found muscle weakness, erythrocyte and leukocyte dysfunction,
causes significant decline in gastrointestinal tract absorption of skeletal demineralization, metabolic acidosis, and nervous system
calcium. There may be frank precipitation of calcium and phos- dysfunction (Table 54-15).
phate, decreasing serum calcium levels further. When the calcium- Before initiating treatment, the cause of hypophosphatemia
phosphorus product exceeds 70mg2/dL2, the risk of abnormal should be clearly identified with measurement of arterial blood
calcification is increased. An elevated calcium phosphorus level gases and the concentrations of ionized calcium, magnesium,
represents poor phosphorus control and often is associated with potassium, and serum and urinary phosphorus. Phosphate salts,
metastatic tissue calcifications. Treatment involves administra- such as sodium and potassium phosphate, are available for oral
tion of phosphate-binding antacids, such as aluminum antacids or intravenous administration. Multiplying the volume of distri-
and sucralfate, calcium citrate, or calcium carbonate, and may bution (400mL/kg) by the desired change in inorganic phosphate
include dialysis, especially in patients with renal failure (Table provides the total amount to be administered. The rate of intra-
54-14). venous administration should not exceed 0.25mmol/kg over 4 to
6 hours to avoid hypocalcemia and tissue damage. Oral supple-
mentation is often limited to 30mmol/day (1g/day) because of
Hypophosphatemia the induction of diarrhea. Hyperphosphatemia should be avoided
because it can cause hypocalcemia and crystal deposition in the
The typical normal range of phosphorus is 2.4 to 4.1mg/dL. eyes, heart, lung, blood vessels, and kidneys. Most hypophos-
Hypophosphatemia has many causes and is severe when serum phatemic patients, such as patients with diabetic ketoacidosis or
phosphorus levels decline to less than 1mg/dL. Conditions recovering from exercise, are not severely phosphorus-depleted,
causing such low phosphate levels include prolonged respiratory unless they have been sick for an extended time. They typically
alkalosis and rapid cellular uptake. Severe hypophosphatemia may be treated with a glass of milk (100mg/dL or 33mmol/L of
with total-body deficiency usually reflects poor dietary intake or phosphorus). After achieving normal serum phosphate levels, the
consumption of phosphate-binding antacids, or both. concentrations of serum inorganic phosphate and ionized calcium
Hypophosphatemia occurs in alcoholism (50% of hospital- and a 24-hour urine sample should be monitored to ensure that
ized alcoholics), refeeding syndrome (commonly in the intensive balance has been achieved.
IV 1716 Anesthesia Management
Table 54-15 Major Causes of Hypophosphatemia min. When controlling blood glucose, close monitoring is crucial.
Reagent strips containing glucose oxidase, used in conjunction
Chronic alcoholism and alcohol withdrawal
with glucometers, provide rapid and reliable results. It is impera-
Dietary deficiency and phosphate-binding antacids
Severe thermal burns
tive to know the insulin regimen or oral hypoglycemic agent of
Recovery from diabetic ketoacidosis each patient and then measure the blood glucose preoperatively,
Hyperalimentation intraoperatively, and postoperatively. The degree of end-organ
Nutritional recovery syndrome damage, coronary artery disease, and autonomic neuropathy can
Respiratory alkalosis contribute to the risk of aspiration, myocardial infarction, and
Therapeutic hyperthermia peripheral neuropathy.
Neuroleptic malignant syndrome
Recovery from exhaustive exercise
Renal transplantation Hyperglycemia
Acute renal failure
Adapted from Potts JT: Diseases of the parathyroid gland and other hyper- and Hyperglycemia (>180 to 200mg/dL) is most often caused by
hypocalcemic disorders. In Isselbacher KJ, Braunwald E, Wilson JD, et al (eds): insulin deficiency, insulin receptor resistance, or glucose overad-
Harrisons Principles of Internal Medicine, 13th ed. New York, McGraw-Hill, 1995, p
2185.
ministration. Hyperglycemia produces osmotic diuresis; exacer-
bation of brain, spinal cord,45 and renal damage46 by ischemia;
delayed gastric emptying47; hypophosphatemia47; delayed wound
Significant hypophosphatemia is common after surgery healing47,48; and impaired white blood cell function.48 Maternal
and can contribute to respiratory and cardiac failure. In one study hyperglycemia increases the risk of neonatal jaundice, the risk of
of elective cardiac surgery, 34.3% of patients had significant hypo- neonatal brain damage, and fetal acidosis if the fetus becomes
phosphatemia. These patients were characterized by prolonged hypoxic.
ventilation, had a larger cardioactive drug requirement, and had Even with supramaximal levels of insulin, adults can use
prolonged hospital stays.43 glucose only at a rate of 3 to 5mg/kg/min at rest (approximately
240mL/hr of 5% solution). The maximal rate of metabolism is
less in stress states and more with increased metabolic rates. Gen-
erally, the rate of administration should be limited to 2 to 3mg/
Chloride Physiology kg/min (120 to 180mg/kg/hr), which is 100g/hr for a 70-kg
person (200mL/hr of a 5% dextrose solution). Healthy infants
Chloride is the predominant anion in the ECF volume. Hyper- and children become hyperglycemic if 5% dextrose is included in
chloremic, metabolic acidosis results from excess intake or inad- maintenance fluids.49 The maximal rate of glucose disposition in
equate excretion because of renal dysfunction. When administering young children is 4 to 8mg/kg/min, and the optimal rate is less
infusions to such patients, bicarbonate, acetate, citrate, or phos- than 5mg/kg/min.50 It is unclear that glucose administration is
phate salts should be substituted for chloride salts. necessary for intraoperative management of most patients.51
Excess loss of chloride in gastric secretions or urine causes
hypochloremic alkalosis. Chloride depletion tends to limit bicar-
bonate excretion, and this may be caused by reduced delivery of
chloride to the collecting tubules, where chloride is needed for Diabetes Mellitus
bicarbonate secretion by means of bicarbonate-chloride exchange.
Sodium reabsorption is enhanced in chloride-depleted states Diabetes mellitus (see Chapter 35) is the most common endo-
because it is generally associated with ECF volume depletion. crine disease and is characterized by long-term complications
When less chloride is available for reabsorption, a greater fraction involving the eyes, kidneys, nerves, and blood vessels. Diabetes is
of the sodium must be reabsorbed with bicarbonate through a major risk factor for heart disease, stroke, kidney disease, blind-
increased proton secretion.44 Sodium or potassium chloride ness, and nontraumatic amputations. The cause of diabetic com-
should be administered if intravascular volume depletion or plications is multifactorial, including glycosylation of proteins
hypokalemia is present. If these are not a problem, 0.1N hydro- and glucose reduction to sorbitol, which functions as a tissue
chloric acid should be administered through a central catheter: toxin. This pathophysiologic process is associated with a decrease
in myo-inositol content and metabolism and with a decrease in
Chloride dose = (Cl desired Cl measured ) 0.2 weight ( kg )
Na+-K+/ATPase activity. Hyperglycemia is recognized as a major
factor in the development of complications associated with dia-
betes. The patient population is not homogeneous, and several
Glucose Physiology and diabetic syndromes have been delineated. There are almost 8
million diagnosed diabetics in the United States and another 8
Fluid Implications million who are unaware of their diabetes. These numbers
approach 10% of the overall U.S. population (Table 54-16).52
Close Monitoring
Glucose is a crucial fuel source, and insulin facilitates glucose Pathology
movement into cells in a process that also requires potassium and
phosphate. Red blood cells, healing wounds, brain, and adrenal Hyperglycemia of diabetes is the consequence of relative or abso-
medulla require glucose for fuel, totaling approximately 2mg/kg/ lute deficiency of insulin and a relative or absolute excess of glu-
Intravascular Fluid and Electrolyte Physiology 1717 54
Table 54-16 Classification of Diabetes pregnancies in the United States, resulting in about 135,000 cases
annually.55 Clinical recognition of gestational diabetes is impor-
Class Causes and Characteristics
tant because therapy and antepartum fetal monitoring can reduce
Primary IDDM, type 1without insulin, the patient develops perinatal morbidity and mortality. Maternal complications related
ketoacidosis and dies to gestational diabetes include an increased rate of cesarean
NIDDM, type 2the patient does not always develop delivery.
ketoacidosis without insulin During the past decade, a new disorder known as syn-
Nonobese NIDDM (type 1 IDDM in evolution?) drome X has been described. As the name implies, it is a syn-
Sulfonylurea therapy Unresponsive Responsive Long acting Protamine zinc 4-8hr 14-24hr 28-36hr
Ultralente 4-8hr 14-24hr 28-36hr
Foster DW: Endocrinology and metabolism. In Wilson JD, Braunwald E, Fauci AS,
et al (eds): Harrisons Principles of Internal Medicine, 12th ed. New York, McGraw- Adapted from Stoelting RK, Dierdorf SF: Endocrine disease. In: Anesthesia and Co-
Hill, 1991, p 1743. Existing Disease, 3rd ed. New York, Churchill Livingstone, 1993, p 340.
IV 1718 Anesthesia Management
Table 54-19 Insulin Analog Comparison allosteric interactions between chains. This alteration in
normal hemoglobin has been shown to decrease oxygen
Brand Onset Peak Duration
saturation and red blood cell oxygen transport in pregnant
Analog Name Manufacturer (min) (hr) (hr)
diabetic patients.64
Lispro Humalog Eli Lilly 5-15 1-2 2-3 2. A common complication of diabetes is autonomic dysfunc-
Glargine Lantus Hoechst- 1-3hr No true 24
tion. Patients in whom diabetes has been poorly controlled
Marion peak for many years often have damage to the autonomic nervous
Roussel for system. One study65 showed that diabetic patients with pre-
Aventis viously diagnosed autonomic dysfunction are at increased
risk for intraoperative hypothermia. The pathogenesis may
Aspart NovoRapid NovoNordisk 5-15 1-2 2-3
be related to inappropriate regulation of peripheral vaso-
constriction to conserve body heat.
3. Autonomic dysfunction also affects the bodys ability to
Insulin therapy can result in anaphylactic and anaphylac- regulate arterial blood pressure, leading to significant
toid reactions, especially when using protamine-containing orthostatic hypotension. This underlying defect is caused
insulin preparations. Protamine-derived insulin is made from fish by a lack of appropriate vasoconstriction. This denervation
sperm and can cause immunologic sensitization when protamine also may involve vagal control of the heart rate. The changes
reversal is administered after cardiopulmonary bypass or heparin in heart rate seen with atropine and -blockers are blunted
reversal.56 The protamine reaction can be devastating and includes in patients with significant autonomic dysfunction.66
profound hypotension, pulmonary vasoconstriction, and noncar- 4. Damage to the autonomic nervous system can significantly
diogenic pulmonary edema. Insulin analogs have been developed affect the choice of anesthetic technique. Patients are at
with improved time-action profiles. significantly increased risk of hypotension caused by induc-
The first insulin analog was introduced in the mid-1990s. tion agents, such as thiopental or propofol. For this reason,
Several other insulin analogs subsequently have been formulated etomidate may be a better induction agent because of
(Table 54-19). Insulin lispro (Humalog) is a genetically engi- its considerably lower incidence of cardiovascular side
neered protein identical to human insulin except for a reversal of effects.
the amino acids, proline and lysine, at positions 28 and 29 of the 5. Diabetes has well-defined adverse effects on the cardiovas-
chain.57 cular system. Men who have diabetes have twice the age-
This reversal in the amino acid sequence allows for a more adjusted risk for coronary artery disease. The risk for
rapid absorption and faster onset of action compared with regular women is tripled, indicating that they may be even more
insulin.58-61 Reversal of the proline-lysine sequence eliminates two sensitive to the cardiovascular effects of diabetes.67 Data
crucial hydrophobic interactions responsible for the -sheet con- show that patients with diabetes may be at even greater risk
formational changes and dimerization. Decreased propensity for for coronary artery disease than was previously suspected.
dimerization is the key to understanding the absorptive charac- One study revealed that patients with type 2 diabetes had
teristics of insulin lispro. as great a risk for myocardial infarction as nondiabetic
Another insulin analog that has been released is insulin patients who already had a previous myocardial infarc-
glargine (Lantus), which resembles the human insulin protein tion.68 This information reinforces the point that diabetic
with addition of two arginine amino acids to the chain and patients must be carefully evaluated preoperatively for
replaces asparagine with glycine at the -21 position. The addi- coronary artery disease. Also, diabetic patients are more
tion of the two arginine units causes a shift in the isoelectric point likely to have silent ischemia. They may not experience the
to 6.7 0.2, which allows for precipitation of the insulin glargine classic chest pain and tightness associated with ischemic
in the neutral pH of human tissue. The substitution of glycine in heart disease. Questions regarding exercise tolerance and
the chain and the addition of 30 g/mL of zinc increase the shortness of breath with exertion may provide important
hexamer stability of the precipitate.62,63 This precipitate slowly information regarding underlying heart disease or the
dissolves and results in a constant time-action profile with no degree of compensation.
pronounced peak. This time-action profile allows for once-daily 6. Diabetes affects the gastrointestinal tract in several ways.
dosing and a duration of action of 18 to 24 hours. These new First, it damages the ganglion cells of the gastrointestinal
preparations are being encountered more often in patients being tract, inhibiting motility, which delays gastric emptying and
assessed for surgery, and understanding their time-action profiles overall transit time through the gut. This increased transit
is essential in clinical management. time has a significant impact on the practice of anesthesia
in that all diabetic patients should be treated as if they have
a full stomach. Preoperative treatment with agents that
Anesthetic Considerations inhibit acid secretion and neutralize stomach acid is essen-
tial. Rapid-sequence induction is commonly employed to
Because diabetes affects multiple organ systems, the perioperative try to minimize this risk of aspiration.
impact can be profound. Several clinically relevant issues should
be considered during perioperative anesthetic management, as Perioperative and intraoperative glycemic-control regi-
follows: mens depend on several factors. First, differentiating type 1 from
type 2 diabetes is crucial. Patients with type 1 diabetes are at risk
1. Diabetes affects oxygen transport by causing glucose to for ketonemia if they are without insulin. The risk of ketosis is
bind covalently to the hemoglobin molecule, and alters the amplified when the patient undergoes the stress of surgery.
Intravascular Fluid and Electrolyte Physiology 1719 54
Second, the degree to which blood glucose levels are controlled stituted only after renal function has been reevaluated and found
long-term affects management. Glycosylated hemoglobin (hemo- to be normal.75,76
globin A1c) is the most accurate way to assess glucose control over The typical sliding scale is destined to fail because it
the previous 2 to 3 months. As levels of hemoglobin A1c increase, involves the administration of a fixed dose after documentation
so does the complication rate of diabetes. The amount of exoge- of hyperglycemia. A small modification improves control. The
nous insulin a patient normally requires is important in deciding selected dose should be administered every 4 to 6 hours, based
how blood glucose should be treated intraoperatively. The mag- on response. If the glucose level is less than 60mg/dL, the dose
nitude of the surgery plays an important role in determining should be with held for at least 1 hour, and 50% dextrose should
1. The bicarbonate is injected initially into the plasma volume Clinical Acid-Base Balance
(about 3L) instead of into the calculated treatable space Disturbances
(21L).
2. When bicarbonate is added to acid, it fizzes. This does not
occur literally in the blood. Nevertheless, most bicarbonate This section provides practical clinical examples to assist in
is converted to carbon dioxide and has to be eliminated. understanding acid-base balance.
For each 100mEq that is converted, about 2.24L of carbon
dioxide has to be exhaled, equivalent to 10 minutes of
normal production.
3. The carbon dioxide that is produced enters the cells freely, Metabolic Acidosis from
in contrast to the bicarbonate ions that have been admin- Low Cardiac Output
istered. The inside of the cell initially may become even
more acid. Direct studies with nuclear magnetic resonance A patient with coronary artery disease and an ejection fraction
have not confirmed this, however (Severinghaus, personal of 15% experienced myocardial perforation while undergoing
communication, 1986). balloon angioplasty in the cardiac catheterization laboratory.
4. The bicarbonate is accompanied by sodium ions that are After resuscitation, intubation, insertion of an arterial line, and
responsible for a residual increase in the osmolality of the initiation of dopamine by infusion, the patient was transferred to
ECF. In combination with other therapy, such as intrave- the operating room for emergency thoracotomy. Blood pressure
nous glucose, the hyperosmolality may be critical and cause was 80/50mmHg, and the heart rate was 120 beats/min. During
coma. In neonates, rapid infusion of bicarbonate may cause preparation for central venous cannulation, the blood pressure
intracranial hemorrhage. decreased, followed by cardiac arrest. The patient underwent
5. If the body deals with its metabolic acidosis, there is a immediate thoracotomy. Blood gas determinations obtained at
residual metabolic alkalosis. the time were as follows: pHa 7.15, Paco2 35mmHg, BE 15mEq/
L, bicarbonate 12mEq/L, and Pao2 90mmHg. These values indi-
cated a severe metabolic acidosis with mild respiratory alkalosis.
Anion Gap After the administration of 4U of packed red blood cells (PRBCs)
and 88mEq of sodium bicarbonate, repeat blood gas determina-
Some causes of metabolic acidosis release anions into the ECF tions were as follows: pHa 7.14, Paco2 39mmHg, BE 14mEq/L,
that are not normally measured. When this occurs, there is bicarbonate 13mEq/L, and Pao2 95mmHg. These values still
an unexpected discrepancy between the sums of the principal indicated a severe metabolic acidosis, but with no respiratory
cations and anions. The usual sum is shown in the following alkalosis.
equation: The first blood gas determination revealed a metabolic aci-
dosis attributable to the low cardiac output with tissue ischemia
Na + + K + = Cl + HCO3 + gap and with slight hyperventilation. The second blood gas determi-
140 + 5 = 105 + 25 + ( 15) nation showed almost no benefit from the bicarbonate, probably
because of continuing low cardiac output. Bicarbonate is con-
When there are any additional, unmeasured anions, they verted to carbon dioxide, which may explain the slightly higher
become part of the gap, which is then correspondingly larger. A level of Paco2.
IV 1722 Anesthesia Management
opathy (see Chapters 82 and 83). After the patient was trans-
Metabolic Acidosis During
ported to the operating room, blood gas analysis showed the
Anhepatic Phase following: pHa 7.27, Paco2 65mmHg, BE 3mEq/L, bicarbonate
29mEq/L, and Pao2 35mmHg. Anesthesia was induced, and ven-
A patient with end-stage liver disease caused by viral hepatitis tilation was controlled, with a tidal volume of 60mL, peak inspir-
underwent orthotopic liver transplantation. Blood gas analysis atory pressure of 25cm H2O, positive end-expiratory pressure of
performed late in the anhepatic phase (see Chapter 67), after 4cm H2O, respiratory rate of 40 breaths/min, no inspiratory
earlier administration of bicarbonate, revealed the following: pHa pause, and Fio2 of 0.3. Repeat analysis of blood gases showed the
7.10, Paco2 28mmHg, BE 18mEq/L, bicarbonate 8.6mEq/L, following: pHa 7.36, Paco2 50mmHg, BE 3mEq/L, bicarbonate
Pao2 260mmHg, and Na+ 153mEq/L. These values indicated a 28mEq/L, and Pao2 48mEq/L.
severe metabolic acidosis with a moderate respiratory alkalosis. The mild metabolic alkalosis of the first analysis is compat-
The patient was treated with 500mL (150mEq, 18g) of 0.3M ible with compensation for chronic respiratory failure. The high
solution of tris(hydroxymethyl)aminomethane (THAM) by infu- Paco2 value represented hypoventilation during transport. Appro-
sion over 20 minutes. Repeat blood gas analysis showed the fol- priate selection of the ventilator settings returned the Paco2 to a
lowing: pHa 7.09, Paco2 30mmHg, BE 18mEq/L, bicarbonate value more typical for a neonate with bronchopulmonary dyspla-
9mEq/L, Pao2 251mmHg, and Na+ 154mEq/L. A second dose sia with a pHa about halfway between no compensation and com-
of THAM was administered by infusion. After transplantation, plete compensation (see Chapters 82 and 83).
blood gas analysis showed the following: pHa 7.30, Paco2
33mmHg, BE 9mEq/L, bicarbonate 16mEq/L, Pao2 283mmHg,
and Na+ 149mEq/L. These values indicated a marked metabolic Preparation for Chronic Hyperventilation
acidosis with a mild respiratory alkalosis typical of a partially
compensated metabolic disturbance. A clinician was a member of a team providing plastic surgery at
The metabolic acidosis during the anhepatic phase showed high altitude. For 2 days preceding the trip, he was advised to take
the importance of the liver in metabolizing lactate to bicarbonate. a carbonic anhydrase inhibitor, acetazolamide, which would effec-
The high sodium militated against repeat administration of tively slow the normal reversible reaction between carbonic acid
sodium bicarbonate. In this case, THAM was used to minimize and its dissociation products, carbonic acid and water. The drug
sodium administration while controlling the metabolic acidosis. alkalinizes the urine and produces a moderate metabolic acidosis,
On reperfusion (phase 3), the new liver started to function, and the typical response to hypoxic hyperventilation at altitude. A
there was improvement in the metabolic acidosis. typical blood gas determination after acclimatization to altitude
shows the following: pHa 7.42, Paco2 31mmHg, BE 4mEq/L,
bicarbonate 19mEq/L, and Pao2 80mmHg.
Metabolic Alkalosis After Diuretics The benefit of taking acetazolamide is debated by climbers,
and the drug is not without side effects. During the initial experi-
A 3-month-old, 4-kg infant boy was presented for repair of an ence of taking acetazolamide at sea level, a striking, if minor, side
atrioventricular canal (see Chapter 83). The patients congenital effect is the metallic taste associated with drinking any carbon-
heart failure had been controlled with digitalis and furosemide. ated beverage, presumably attributable to the inability to convert
Before induction of anesthesia, blood gas analysis showed the the high carbon dioxide content in the beverages to carbonic
following: pHa 7.53, Paco2 44mmHg, BE 14mEq/L, bicarbonate acid.
35.9mEq/L, and Pao2 110mmHg. These values showed a severe
metabolic alkalosis with a minimal respiratory acidosis typical of
a partially compensated metabolic disturbance. After induction
of anesthesia, blood gas analysis showed the following: pHa 7.61, Acute Hyperventilation and Hypotension
Paco2 35mmHg, BE 14mEq/L, bicarbonate 34mEq/L, and Pao2
60mmHg. After completion of the procedure and cessation of A 5-ft, 48-kg elderly woman had an arterial blood pressure of
cardiopulmonary bypass, the blood gas analysis showed the fol- 115/75mmHg and heart rate of 70 beats/min (see Chapter 71).
lowing: pHa 7.40, Paco2 33mmHg, BE 4mEq/L, and bicarbo- She was receiving no medications and was in otherwise normal
nate 20mEq/L. health. She was scheduled for a laparotomy and hysterectomy.
The hypochloremic alkalosis that accompanies prolonged After induction of anesthesia and orotracheal intubation, control-
administration of furosemide explains the first set of results. After led ventilation was initiated with a tidal volume of 900mL and a
induction of anesthesia, the hyperventilation decreased the Paco2, respiratory rate of 12 breaths/min. Shortly before incision, the
but had no effect on the base excess. Two major factors explain arterial blood pressure was 58/35mmHg, and the end-tidal Pco2
the change during the procedure. Hemodilution tends to return was 22mmHg. (Blood gases were not tested, but typical values
the pHa toward neutral (6.8 at body temperature), and low per- for a patient experiencing such acute hyperventilation are as
fusion during bypass frequently produces a metabolic acidosis follows: pHa 7.53, Paco2 26mmHg, bicarbonate 21mEq/L, and
that, in this case, also helped to overcome the initial metabolic BE 0mg/L.)
alkalosis. The ventilator was immediately reset to provide 4 breaths/
min at a tidal volume of 500mL. Arterial blood pressure about 2
Chronic Respiratory Failure in a Neonate minutes later was 85/55mmHg, and the next reading about 2
A 2.5-month-old, 3.5-kg infant boy with bronchopulmonary dys- minutes later still was 95/65mmHg. The patients end-tidal Pco2
plasia was tracheally intubated and received supplemental oxygen increased more slowly, and after about 8 minutes, it had returned
(Fio2 0.3). He presented for cryoablation for proliferative retin- to 36mmHg when the ventilatory rate was increased to 8 breaths/
Intravascular Fluid and Electrolyte Physiology 1723 54
min. (Typically, her blood gas values would be near-normal, such solution recommendations applicable to typical surgical and
as pHa 7.44, Paco2 38mmHg, bicarbonate 23.3mEq/L, and BE obstetric patients (Table 54-20). Information about infants, chil-
0mg/L). Hyperventilation after induction is common and fre- dren, and special clinical settings can found elsewhere in this
quently contributes to hypotension by various methods, includ- book (see Chapter 82).
ing increased intrathoracic pressure, diminished venous return,
and depressed cardiac output.
FFP 15.4
*The range of values refers to concentrations on day 1 and day 21 (CPD), 35 (CPDA-1), or 42 (AS-1) of storage.
Fructose substituted for dextrose.
COP, colloid oncotic pressure; D5LR, 5% dextrose in lactated Ringer solution; D50.45% NaCl, 5% dextrose in 0.45% sodium chloride; FFP, fresh frozen plasma; Hct, hematocrit;
Mg, magnesium; PRBC, packed red blood cells.
In normal patients, the body maintains a balance between varies depending on the organ being measured. Venous blood
delivery of oxygen (Do2) and global oxygen consumption (Vo2). returning from the liver has a saturation of 40% to 50%, and blood
Global oxygen consumption is a measure of the total amount of from the kidneys may have a saturation greater than 80%.
oxygen consumed by all tissues per minute. The amount of oxygen Oxygen consumption is directly related to cellular meta-
consumed as a fraction of the amount delivered defines the bolic rate. Sympathetic activity, shivering, and physical activity all
oxygen extraction ratio (OER): increase the cellular metabolic rate. As the delivery of oxygen
decreases or the consumption increases, the OER increases to
OER = VO2 DO2
maintain aerobic metabolism. The OER can increase to approxi-
Vo2 in a normal adult undertaking routine activities is mately 60% to 70%, at which point further increase in consump-
approximately 250mL/min with an extraction ratio of 25%. The tion or decrease in delivery results in tissue hypoxia and anaerobic
OER can be increased to 75% during extreme exercise in a healthy metabolism.
adult. Oxygen not extracted from the blood returns to the lungs Tissue hypoxia and shock can result from inappropriate
and can be measured as the mixed venous saturation (Svo2), delivery of cellular oxygen or inappropriate cellular use of oxygen.
which is a measure of global tissue oxygenation. Svo2 less than There are two distinct types of shock. Type I involves patients who
60% to 70% usually indicates insufficient Do2. A mixed venous experience decreased delivery of oxygen, such as in hypovolemic
blood sample is needed because the saturation of venous blood or cardiogenic shock. Type II involves problems with inappropri-
Intravascular Fluid and Electrolyte Physiology 1725 54
ate distribution of oxygen delivery, such as in septic or neurogenic Compared with 0.9% NaCl, these solutions provide small quanti-
shock. Regardless of the underlying cause, appropriate fluid man- ties of other electrolytes, which are inadequate to meet daily
agement is an absolute necessity. maintenance requirements.
Proper fluid management of shock can have a significant
impact on the delivery of oxygen to tissues and prevention of
anaerobic metabolism. Until more recently, vigorous fluid loading Normal Saline
and inotropic agents were commonly used in what was called
goal-directed therapy during the care of critically ill patients. Normal saline (0.9% NaCl) is isotonic and iso-osmotic, but con-
plasma volume rapidly. Results can be achieved with 250mL of brane. Typical values for plasma proteins in the microvascula-
7.5% saline that are comparable to resuscitation with 2 to 3L of ture exceed 0.9 in most organs, and these values remain constant,
0.9% saline.87 Larger, randomized controlled studies are needed but can be decreased significantly by pathophysiologic processes,
to evaluate thoroughly its use in standard practice. In this regard, including hypoxia, inflammation, and tissue injury. COPM is the
to date, improved rates of survival with hypertonic saline were colloid oncotic pressure, and COPT is the colloid oncotic pressure
reported in seven of eight clinical trials, although statistically in the tissue.
significant improvement in overall survival was seen in only one The hydrostatic and colloid pressure differences across
trial.87 capillary walls (i.e., Starling forces) cause movement of water
and dissolved solutes into the interstitial spaces. These move-
ments play a minor role with regard to tissue nutrition relative to
Five Percent Dextrose simple diffusion. The reflection coefficient that expresses the
ability of the semipermeable membrane to prevent movement of
Five percent dextrose functions as free water because the dextrose a solute varies greatly among tissues. The lungs are moderately
is metabolized. It is iso-osmotic and does not cause the hemolysis permeable relative to other organs, and during pathophysiologic
that would occur if pure water were injected intravenously. processes such as surgical trauma, the reflection coefficient
Although it may be used to correct hypernatremia, 5% dextrose may change further to alter capillary permeability, resulting in
is most often used in the prevention of hypoglycemia in diabetic increased capillary permeability or leak. In this setting, colloids
patients who have had insulin administered. move more easily into the interstitium and increase interstitial
edema.
With leakage of colloid molecules into the interstitial space,
Crystalloids Versus Colloids further swelling of tissues occurs because of the unfavorable
oncotic pressure gradient, and these molecules are removed by
Much controversy exists about the role of crystalloids and colloids the lymphatic system. Removal of colloids requires longer periods
in fluid therapy (see Chapters 55 and 88). Proponents of colloid than for crystalloids and can be a significant problem in burn
fluid point out that resuscitation with crystalloid solution dilutes patients and patients undergoing major surgery. A well-known
the plasma proteins, with a subsequent reduction of plasma meta-analysis by Velanovich101 of mortality from eight studies
oncotic pressure resulting in fluid filtration from the intravascular published in 1989 concluded that trauma patients should be
to the interstitial compartment and the development of interstitial resuscitated with crystalloid solutions, whereas colloids were
pulmonary edema. Proponents of crystalloid solutions have more effective in nonseptic, nontraumatic, elective surgical
argued that albumin molecules normally enter the pulmonary patients. Current data seem to support the concept that blood
interstitial compartment freely and then are cleared through the composition should be maintained as close to normal as possible
lymphatic system returning to the systemic circulation. Addi- in terms of directed transfusion of red blood cells and coagulation
tional albumin should merely increase the albumin pool cleared factors.86
by the lymphatics. A review of the literature by Moss and Gould100 Another factor that must be considered is the overall effect
confirmed that all unflawed clinical and experimental studies of resuscitation fluid on the coagulation cascade. It is a well-
showed that isotonic solutions are effective plasma volume known phenomenon that after trauma, patients may have low
expanders for resuscitation without the addition of a variety of levels of circulating coagulation factors. This deficiency may lead
colloid fluids. The additional cost and potential risks of colloids to transfusion of fresh frozen plasma to restore deficient factors.
compared with crystalloids is another argument against colloid The clotting cascade is an extremely complex string of events,
administration. with many factors affecting the progression to clot. Studies using
Colloids used in the United States include albumin, hydrox- a thromboelastogram to measure trauma patients clotting status
yethyl starch (hetastarch), and dextran. Because the molecules are have indicated that these patients may be hypercoagulable.102
large, colloids usually do not cross capillary membranes and Another study using thromboelastographic profiles showed that
remain intravascular. Distribution of fluid throughout the body patients undergoing major surgery who were given intraoperative
is represented by the Starling-Landis equation: lactated Ringers solution also were hypercoagulable compared
with baseline.103 These studies suggest that the type of fluid used
J v = K h A ([ PM PT ] [COPM COPT ]) for volume resuscitation may play a role in the coagulopathy often
seen in trauma patients (see Chapter 56). Definitive studies are
In this equation, Jv represents the net volume of fluid still needed, however, to elucidate the true impact that resuscita-
moving across the capillary wall per unit of time, expressed as tion fluids play in the coagulation cascade.
m3/min; Kh is the hydraulic conductivity for water, which is the
fluid permeability of the capillary wall, expressed as m3/min per
square micrometer of capillary surface area per 1mmHg pres-
sure difference. The value of Kh increases up to fourfold from the
arterial to the venous end of a typical capillary. PM is the capillary
hydrostatic pressure; PT is the tissue hydrostatic pressure; A is the
Colloid Solutions and Blood
capillary surface area; and is the reflection coefficient for plasma Substitutes
proteins. This coefficient is necessary because the plasma proteins
are slightly permeable to the microvascular wall, preventing full Colloid solutions generally are administered in a volume equiva-
expression of the two COPs. When is 0, molecules cross the lent to the volume of blood lost (see Chapter 55). The initial
membrane freely; when is 1, molecules cannot cross the mem- volume of distribution is equivalent to the plasma volume. The
Intravascular Fluid and Electrolyte Physiology 1727 54
half-life in circulation of albumin is normally 16 hours, but it can the reticuloendothelial system for several hours and is believed
be only 2 to 3 hours in pathophysiologic conditions.104 The syn- to be renally excreted. It produces dilutional effects similar to
thetic colloids, processed albumin, and protein fractions have other volume expanders and reduces factor VIII:C and vWF
minimal or no risks of infection. Blood substitutes are useful to levels by 50% to 80% in a dose of 1 to 1.5L, with prolongation of
restore intravascular fluid volume temporarily until definitive the partial thromboplastin time.106 Hetastarch also can interfere
treatment can be established. They are inexpensive, have a long with platelet adhesion and clot formation by reduction in
storage life, and lack the risk of transmitting viral diseases. glycoprotein IIb/IIIa availability and direct movement of the
hetastarch molecules into the fibrin clot.106 In clinically recom-
The following guidelines are intended to facilitate initiating Saliva 500-2000 2-10 20-30 8-18 30
therapy, but the choice of fluid and rate of administration must Stomach 1000-2000 60-100 10-20 100-130 0
be adjusted to achieve physiologic goals. These guidelines are only
a starting point for patients without other major comorbid dis- Pancreas 300-800 135-145 5-10 70-90 95-120
eases of vital organs. Careful observation of the patients response Bile 300-600 135-145 5-10 90-130 30-40
forms the basis for ongoing modification in a continuous feed-
Jejunum 2000-4000 120-140 5-10 90-140 30-40
back loop.
Ileum 1000-2000 80-150 2-8 45-140 30
Colon 60 30 40
Routine Maintenance Fluids
Routine maintenance fluids are described for a 70-kg postopera-
tive patient. The patient requires 110mL H2O and 110kcal/hr, or
2640mL and 2640kcal/day. This example is based on the 4-2-1 The osmolarity of 7.5% dextrose is 417mOsm/L, to which is
rule (Table 54-21), which provides a close approximation of water added 156mOsm/kg H2O, resulting in a highly hyperosmolar
requirements. The sodium requirement (1.5mEq/kg/day) is dis- solution. A compromise between the need for glucose and hyper-
solved in the daily fluid requirement of 2.64L; the 100mEq/kg/ osmolality has been 5% dextrose.
day requirement for potassium is placed in the 2.64L/day water If there are other losses (e.g., gastric drainage), additional
requirement: 100mEq K/2.64L = 42mEq/L. The potassium con- sodium and water are required. Gastric drainage of 0.5L/day
centration needs to be limited, however, if the fluid is to be infused loses 30 to 50mEq of sodium and 50 to 65mEq of chloride (Table
into a peripheral vein because of the chemical irritation induced 54-22). When these are added to the maintenance fluid, the con-
by high concentrations of potassium. centration approximates 0.45% NaCl. This solution is commonly
The long-standing concept first presented in 1957 by Holli- used as a maintenance intravenous fluid postoperatively in
day and Seger of the 4-2-1 rule for crystalloid delivery has been patients with nasogastric drainage.
challenged more recently. The focus of this challenge is on reduc-
tion of free water administration because of increased postopera-
tive hyponatremia related to increased secretion of ADH. An Routine Intraoperative Fluid Administration
alternative concept is for much lower glucose administration and
isotonic sodiumcontaining solutions to avoid the rare problem The goals of intraoperative fluid administration are to maintain
of hyponatremic seizure and brain damage (seen mainly in adequate oxygen delivery, normal electrolyte concentrations, and
children).107 normoglycemia. The total fluid requirement is composed of com-
The obligatory glucose needs of the brain and red blood pensatory intravascular volume expansion (CVE), deficit replace-
cells are roughly 2 mg/kg/min. Because dextrose contains ment, maintenance fluids, restoration of losses, and substitution
3.41kcal/g instead of 4kcal/g of glucose, about 17% more dex- for fluid redistribution (i.e., third space fluids):
trose than glucose is required. If carbohydrate is not provided,
Rate of fluid = CVE + deficit + maintenance administration +
glycogenolysis and gluconeogenesis from amino acid pools
loss + third space
provide the necessary glucose, but accelerate protein
catabolism.
Carbohydrate is said to prevent catabolism (i.e., protein
sparing), but the benefit of this dose of dextrose is unclear. Total Compensatory Intravascular
starvation may be preferable because insulin concentrations Volume Expansion
decrease to very low levels, facilitating lipolysis as a caloric source.
Intravascular volume usually must be supplemented to compen-
sate for the venodilation and cardiac depression caused by
Table 54-21 Calculations of Fluid Requirements by 4-2-1 Rule*
anesthesia. Sustaining adequate oxygen delivery in relation to
oxygen consumption is an important goal of fluid therapy. Tissue
Body Weight Fluid Rate Weight Category Fluid oxygen delivery depends on hemoglobin concentration, oxygen
(kg) (mL/kg) (kg) (mL/hr) tension, organ perfusion pressures, and organ vascular resistance.
0-10 4 10 40
Organ perfusion pressures depend on systemic arterial pressure
and the higher of organ venous pressure or tissue pressure. Arte-
11-20 2 10 20 rial pressure depends on cardiac output and systemic vascular
>21 1 5 5 resistance. Cardiac output is related to stroke volume and heart
rate, and stroke volume depends on preload, contractility, and
Total 25 65 afterload. Most general and regional anesthetics cause arteriolar
*Assumes a patient weighing 25kg, resulting in an estimated fluid requirement of and venous dilation, expanding the vascular capacity. The latter
65mL/hr. reduces peripheral venous pressure and venous return and cardiac
Intravascular Fluid and Electrolyte Physiology 1729 54
output. Fluid must be administered to expand the blood volume of blood lost, 1mL of colloid solution should be administered to
to compensate for venodilation. provide improvement of filling pressures, arterial blood pressure,
General anesthetics produce myocardial depression (see and heart rate. PRBC infusions are used at roughly 1mL for each
Chapter 23). Increasing cardiac preload by infusing fluid intra- 2mL of blood lost plus crystalloid or colloid, as previously
vascularly to take advantage of the Starling mechanism often described. Although the effect on volume is 1:1, the hematocrit
returns stroke volume to an acceptable range. Postoperatively, of PRBCs (60% to 70%) is about twice the necessary hematocrit
venodilation and myocardial depression rapidly subside when of the patient. In patients with reasonable cardiac reserve and
administration of the anesthetic is stopped. Patients with impaired without compromised regional circulations (e.g., coronary, cere-
*Reflects fluid replacement for blood loss. Preinduction phase lasts 15 to 20 minutes.
Total fluid administered during the hour.
Grand total since beginning of the case.
Preinduction phase lasts 15 to 20 minutes.
Induction until intra-abdominal surgical entry (assumed to be 1 hour).
Operative time.
replacement fluid. The volume redistributed correlates roughly modified accordingly. Otherwise, the choice and volumes of fluid
with the degree of tissue manipulation. Intra-abdominal proce- are as described for an adult.
dures with small incisions (e.g., hysterectomy) may require an
additional 2mL/kg/hr, whereas a major bowel resection requires
an additional 4 to 6mL/kg/hr.
Table 54-23 describes the fluid management, starting with Postoperative Patient with
a hemoglobin level of 15g/dL, for a 70-kg patient undergoing Bowel Obstruction
gastrectomy who has been fasting for 10 hours. The maintenance
rate is 110mL/hr, producing a deficit of 1100mL. Patients with bowel obstruction are often older and have limited
During the first and second hours of intra-abdominal reserves in several organ systems. Estimating the degree of loss
activity, 100mL of blood was lost and replaced at a 3:1 rate with of fluids is difficult because fluid is retained in the bowel lumen,
a balanced salt solution. By the fourth hour, the deficit had been where it cannot be measured. The slowly developing volume
replaced, and because the abdomen was being closed during part depletion allows time for full expression of compensatory mecha-
of that hour, the estimate of third space losses was likewise nisms that mask the degree of the deficit. Patients have often
reduced, and no further blood loss occurred. The assumption is ingested no fluids for many hours before entering the hospital and
made that urine flow was 50 to 80mL/hr, and that heart rate and are often vomiting. The patient may have ischemic bowel injury
arterial blood pressure were in an acceptable range, and the CVP with severe bowel wall edema and continued sequestration of
remained 6 to 9mmHg. Had the CVP or urine output begun to luminal fluid and formation of ascites. Perioperative fluid intake
increase, the rate of fluid administration would have been slowed. is much larger than measured output, leading consultants to
If oliguria and tachycardia had occurred, a fluid bolus would have suggest diuresis for fluid overload. Nutrition is impaired preop-
been administered. eratively, and protein losses into the bowel are increased, leading
to hypoalbuminemia and exacerbating the loss of fluid from the
vascular space. The clinical picture is one of ongoing fluid require-
Pediatric Patient ment in the absence of external fluid loss, commonly referred to
as third spacing.
There are few special considerations relevant to pediatric fluid The goals of fluid management in this group are similar to
management in addition to those for adults (see Chapter 82). the goals for other patients and include restoration of the vascular
Neonates have limited ability to dilute or concentrate urine and volume and interstitial volume, correction of electrolyte deple-
have a high fluid requirement. Neonates should not be without tion, correction of acidosis, reduction of systemic vascular resist-
fluid for more than 3 to 4 hours; otherwise, significant dehydra- ance into the normal range, and optimization of oxygen delivery
tion may result. Food should be offered until 6 to 8 hours before and use. Initial fluid infusion can restore intravascular volume
anesthesia induction, and glucose-containing clear liquids should sufficiently for blood pressure and heart rate to improve. Intra-
be given about 4 hours before induction. Clear liquids are defined vascular volume still may be depleted, however, with a low cardiac
as transparent liquids that do not contain particulate material or output and severe arterial and venous vasoconstriction. The ECF
protein, which coagulate in the acid medium of the stomach. volume (except for the bowel) remains dehydrated and continues
Using the same principles as outlined for adults, a neonate requires to accept fluids from the vascular space. A patient with vasocon-
maintenance fluids of 0.3% NaCl with potassium. Dextrose striction fails to perfuse all tissues, limiting the rate at which the
administration should not exceed 5mg/kg/min. This requirement ECF volume can be replenished. If fluids are infused more rapidly
generally can be met by using 2.5% dextrosecontaining fluids. than the rate at which they can enter the ECF volume, increased
During extensive, prolonged procedures, blood glucose should be filling pressures may result in pulmonary edema. It is crucial to
monitored, and the rate of dextrose administration should be estimate filling pressures, cardiac output, and systemic vascular
Intravascular Fluid and Electrolyte Physiology 1731 54
resistance while aggressive intravascular fluid with balanced activity because of failure of the liver to metabolize aldosterone.
salt solution and colloid is pursued. It may be necessary to admin- Given the ECF volume expansion, the distribution into ascites
ister arterial vasodilators, such as nitroprusside, to facilitate and tissue edema is explained by the abnormally high portal
correction. venous pressures and hypoalbuminemia. Abnormalities of ANP
Management of a typical patient includes frequent moni- have been investigated. ANP levels are normal or low in cirrhotic
toring of arterial blood pressure, heart rate, CVP, pulse pressure, patients; this contrasts with the increase usually found in volume-
respiratory variation, urine output, and electrolytes. If these expanded patients.113 ANP increased with water immersion or
parameters are stable, the hemoglobin level and COP should be fluid administration, but natriuresis was not closely correlated
dopamine, norepinephrine, phenylephrine, or vasopressin may be Ionized calcium must be measured and corrected routinely. Severe
performed in hypotensive patients with low vascular resistance hypophosphatemia often coexists with abnormalities of calcium,
and hypotension to increase renal perfusion pressure and renal potassium, and magnesium, and leads to depressed contractility.
blood flow.
(
Lactated Ringers solution at 0.25 mL kg [% BSA-burned ] ) and epinephrine solution. This is referred to as the tumescent
hr for 8 hours technique and tends to be used to remove smaller volumes of fat
(<3000mL). Infiltration of large fluid volumes is used to make
(
Lactated Ringers solution at 0.125 mL kg [% BSA-burned ] ) the tissue firm and to facilitate removal of adipose tissue. Because
hr for 16 hours of the smaller volumes of fat removed and less damage to subcu-
taneous tissue, the tumescent technique has less risk of large fluid
(
5% dextrose in water at 0.8 mL kg [% BSA-burned ] ) shifts. Semitumescent liposuction tends to involve removal of
(
hr plus 5% albumin at 0.015 mL kg [% BSA-burned ] ) larger volumes of fat, larger volumes of lidocaine plus epineph
rine solution, and more sedation. When a volume of more than
hr for 24 hours
2000 to 3000mL of fat is removed, the patient may require general
anesthesia. These cases may lead to life-threatening complications
A 50-kg person with 50% BSA burn should receive fluids involving fluid management. Ideally, the epinephrine in the
equal to (50kg) (0.25mL/kg) (50% BSA-burned), or 625mL/ tumescent solution decreases systemic absorption of the extremely
hr for 8 hours. This is followed by fluids equal to (50kg) large volumes of fluid administered subcutaneously. If the fluid is
(0.125mL/kg) (50% BSA-burned), or 310mL/hr for 16 hours. not removed before the effect of the epinephrine has worn off,
During the second 24 hours, fluids administered equal (50kg) however, the patient can absorb a significant amount of the
(0.08mL/kg) (50% BSA-burned), or 200mL/hr of 5% dextrose administered fluid. Case reports120-122 have described the develop-
in water, plus (50kg) (0.015mL/kg) (50% BSA-burned), or ment of pulmonary edema after liposuction.
37.5mL/hr of 5% albumin. Colloids are not contraindicated, even Complicating the management of liposuction patients
during the acute phase of fluid resuscitation. Although they pass further are the large doses of lidocaine administered. During this
into the injured tissue at an accelerated rate, they have a more procedure, patients receive 70 to 80mg/kg of lidocaine. Vasocon-
sustained effect on plasma volume than crystalloid alone. striction and removal of most of the infused solution is thought
to prevent lidocaine toxicity.123 One report124 suggested, however,
that lidocaine might impair alveolar epithelial fluid clearance.
Pregnant Patient with Preeclampsia This impaired clearance of pulmonary fluid in conjunction with
increased intravascular volume from the absorbed solution may
Goals of fluid management in a pregnant patient with preeclamp- explain some of the adverse occurrences, including death, reported
sia (see Chapter 69) are to restore the contracted intravascular after liposuction. There are significant data to support the increase
volume,119 avoid excessive intravascular fluid administration in the maximum dose of lidocaine from the standard 7mg/kg,
because of normal postpartum fluid mobilization, replace but the maximum safe dosage of lidocaine for tumescent liposuc-
increased sensible (sweat) and insensible (respiratory) losses tion is still controversial.
resulting from labor, be prepared to replace rapid blood loss, The American Academy of Dermatology has published
avoid hypotension resulting from anesthetic-induced vasodila- guidelines for liposuction.125,126 The use of significant amounts of
tion to preserve uteroplacental flow, maintain normoglycemia, intravenous sedation or analgesic administration was considered
avoid decreasing the COP further, and prevent pulmonary and to be potentially dangerous, particularly when conducted in an
cerebral edema. Restoration of depleted plasma volume to normal office-based setting. The recommended maximum dose of lido-
is crucial for control of hypertension and for administration of caine was 55mg/kg. This increased dosage mandates proper
anesthesia. Plasma volume is decreased in preeclamptic patients preoperative evaluation of patients medications to determine
because of elevated lower body venous pressure from uterine whether they are using any drugs that inhibit the cytochrome 3A4
compression, pressure-induced natriuresis as seen in hyperten- or 1A2 system. These are the major pathways by which lidocaine
sion, severe vasoconstriction, and hypoproteinemia owing to pro- is metabolized, and even mild inhibition of these enzyme systems
teinuria. After parturition, the fluid retained during pregnancy is can lead to potentially lethal serum lidocaine levels.
usually quickly mobilized and excreted. The preeclamptic patient Controlled trials regarding the best method for performing
may have compromised hepatic, renal, or cardiac function, liposuction are lacking. A large body of practical knowledge sug-
however, impeding the timely excretion of this fluid. These gests, however, that liposuction can be performed safely using
patients are at risk for pulmonary edema because of cardiac large doses of lidocaine and large volumes of infused solution.
failure secondary to severe hypertension and lowered COP. Vigilance regarding potential volume overload and pulmonary
Cardiac filling pressures should be monitored, and a PAOP of less edema is required to perform this procedure safely.
than 12 to 15mmHg should be maintained. Plasma tonicity must
be maintained by administration of isotonic fluid because these
patients are at risk for cerebral edema.
Intravascular Volume Resuscitation of
Patient in Hemorrhagic Shock
Patient Undergoing Liposuction
The urgent priorities for the resuscitation of a seriously bleeding
Patients undergoing liposuction pose unique challenges in regard patient are (1) ensuring an adequate airway, (2) ensuring adequate
to intraoperative fluid management (see Chapter 64). A major respiration, and (3) supporting the circulation. Stopping blood
factor determining the amount of intravascular volume changes loss is most often achieved through manual pressure on the bleed-
during surgery is the type of liposuction being performed. Lipo- ing site or operative intervention (rarely arterial tourniquet appli-
suction can be an office-based procedure using minimal sedation cation), or both. Formerly, intravenous crystalloid (United States)
and subcutaneous infiltration of large volumes of dilute lidocaine or colloid (Europe) solution was administered to normalize blood
Intravascular Fluid and Electrolyte Physiology 1735 54
pressure. More recently, such intravenous fluids have been admin- the more histotoxic of the two in the event of extravasation)
istered at rates just sufficient to maintain arterial systolic blood should be administered to counteract the calcium-binding effects
pressure between 80 and 100mmHg (with some centers limiting of the citrate in blood products if (1) laboratory or bedside moni-
total infused volume during emergency medical services trans- toring reveals a low ionized calcium level, (2) the patient receives
port to 1 to 2L of balanced salt solution [permissive hypoten- blood products at a rate of 10 combined units of PRBCs and fresh
sion]).86 Benefits of this approach (achieved at the expense of frozen plasma per hour, (3) hepatic function (cirrhosis) or hepatic
nonvital organ hypoperfusion and lactic acidosis) include mini- blood flow (high aortic cross-clamp) is compromised, or (4)
mizing (1) the rate of additional blood loss, (2) hypothermia from hypotension remains unresponsive to apparently adequate volume
References
1. Rhoades RA, Tanner GA: Medical Physiology. 5. Herrmann H, Dzau V: The feedback regulation of 9. Reid I: The renin-angiotensin system and body
Boston, Little, Brown, 1995. angiotensinogen production by components of function. Arch Intern Med 145:1475, 1985.
2. Fall PJ: Hyponatremia and hypernatremia: A sys- the renin-angiotensin system. Circ Res 52:328, 10. Reid I: Actions of angiotensin II on the brain:
tematic approach to causes and their correction. 1983. Mechanisms and physiologic role. Am J Physiol
Postgrad Med 107:75, 2000. 6. Clauser E, Bouhnik J, Coezzy E, et al: Synthesis and 246:F533, 1984.
3. Coran AG: Perioperative care of the pediatric release of immunoreactive angiotensinogen by rat 11. Kost C: Effect of angiotensin II on plasma adeno
patient. Surg Ann 23(Pt 1):31, 1991. liver slices. Endocrinology 112:1188, 1983. sine concentrations in the rat. J Cardiovasc Phar-
4. Barajas L, Powers K: The structure of the juxta- 7. Campbell D: The site of angiotensin production. J macol 17:838, 1991.
glomerular apparatus (JGA) and the control of Hypertens 3:199, 1985. 12. Ferrario C, Santos R, Brosnihan K, et al: A hypoth-
renin secretion: An update. J Hypertens 2:3, 8. Ganong W: The brain renin-angiotensin system. esis regarding the function of angiotensin peptides.
1984. Annu Rev Physiol 46:17, 1984. Clin Exp Hypertens 10A:107, 1988.
IV 1736 Anesthesia Management
13. Zubrow AB, Daniel SS, Stark RI, et al: Plasma renin, 35. Allon M, Takeshian A, Shanklin N: Effect of insu- cardiac catheterization. Circulation 70:788,
catecholamine, and vasopressin during nitroprus- lin-plus-glucose infusion with or without epine- 1984.
side-induced hypotension in ewes. Anesthesiology phrine or fasting hyperkalemia. Kidney Int 43:212, 57. Humalog (insulin lispro) package insert. Indiana-
58:245, 1983. 1993. polis, IN, Eli Lilly, 2001.
14. Agre P: Aquaporin water channels in kidney. J Am 36. Holick MF, Krane SM, Potts JT: Calcium, phospho- 58. Kucera ML, Graham JP: Insulin lispro, a new
Soc Nephrol 11:764, 2000. rus, and bone metabolism: Calcium-regulating hor- insulin analog. Pharmacotherapy 18:526, 1998.
15. Nielsen S, Kwon TH, Christensen BM, et al: Physi- mones. In Isselbacher KJ, Braunwald E, Wilson JD, 59. Dimarchi RD, Chance RE, Lon HB, et al: Prepara-
ology and pathophysiology of renal aquaporins. J et al (eds): Harrisons Principles of Internal tion of an insulin with improved pharmacokinetics
Am Soc Nephrol 19:647, 1999. Medicine, 13th ed. New York, McGraw-Hill, 1994, relative to human insulin through consideration of
16. Jensen V: The TURP syndrome. Can J Anaesth p 2139. structure homology with insulin like growth factor
38:90, 1991. 37. Vivien B, Langeron O, Morrell E, et al: Early hypo 1. Horm Res 41(Suppl 2):93, 1994.
17. Pasini A, Belloni C: Intraoperative complications of calcemia in severe trauma. Crit Care Med 33:1946, 60. Howey DC, Bowsher RR, Brunelle RL, Woodworth
697 consecutive operative hysteroscopies. Min 2005. JR: Lys(B28) Pro(B29) human insulin: A rapidly
Ginecol 53:13, 2001. 38. Harris MNE, Crowther A, Jupp RA, et al: Magne- absorbed analog of human insulin. Diabetes 43:396,
18. Moses AM, Blumenthal SA, Streeten DH: Drugs sium and coronary revascularization. Br J Anesth 1994.
and water metabolism. In Arieff AI, Defronzo FA 60:779, 1988. 61. Ciszak E, Beals JM, Frank BH, et al: Role of C-ter-
(eds): Fluid, Electrolyte and Acid-Base Disorders, 39. Kamalanathan S, Vijayan A: Fluid and electrolyte minal B-chain residues in insulin assembly: The
vol 1. New York, Churchill Livingstone, 1985, p management. In Cooper DH, Krainik AJ, Lubner SJ, structure of Hexameric Lys(B28) Pro(B29) human
1145. et al (eds): The Washington Manual of Medical insulin. Structure 3:615, 1995.
19. Zaloga GP, Prough DS: Fluids and electrolytes. In Therapeutics, 32nd ed. Philadelphia, Lippincott 62. Lantus (insulin glargine) package insert. Kansas
Barash PG, Cullen BF, Stoelting RK (eds): Clinical Williams & Wilkins, 2007, p 89. City, MO, Aventis Pharmaceuticals, April 2000.
Anesthesia, 2nd ed. Philadelphia, JB Lippincott, 40. James MFM: Clinical use of magnesium infusions 63. Heinemann L, Linkeschova R, Rave K, et al: Time
1992, pp 214-236. in anesthesia. Anesth Analg 74:129, 1992. action profile of the long-acting insulin analog
20. Gravenstein D: Transurethral resection of prostate 41. Cross HS, Debiec H, Peterlik M: Mechanism and insulin glargine (HOE 901) in comparison with
(TURP) syndrome: A review of the pathology and regulation of intestinal phosphate reabsorption. those of NPH insulin and placebo. Diabetes Care
management. Anesth Analg 84:438, 1997. Miner Electrolyte Metab 16:115, 1990. 23:644, 2000.
21. Ayus JC, Wheeler J, Arieff AI: Postoperative 42. Rhoades RA, Tanner GA: Medical Physiology. 64. Madsen H, Ditzel J: Changes in red blood cell
hyponatremic encephalopathy in menstruant Boston, Little, Brown, 1995. oxygen transport in diabetic pregnancy. Am J
women. Ann Intern Med 117:891, 1992. 43. Cohena J, Koganb A, Saharb G, et al: Hypophos- Obstet Gynecol 143:421, 1982.
22. Fraser CL, Sarnacki P: Na+/K+ ATPase pump func- phatemia following open heart surgery: Incidence 65. Kitamura A, Hoshino T: Patients with diabetic neu-
tion in male rat brain synaptosomes is different and consequences. Eur J Cardiothorac Surg 26:306, ropathy are at risk of a greater intraoperative reduc-
from that of females. Am J Physiol 257:E284, 2004. tion in core temperature. Anesthesiology 92:1311,
1989. 44. Levinsky NG: Acidosis and alkalosis. In Isselbacher 2000.
23. Black RM: Disorders of serum sodium and serum KJ, Braunwald E, Wilson JD, et al (eds): Harrisons 66. Tsueda K, Huang KC, Dumond SW, et al: Cardiac
potassium. In Rippe JM, Irwin RS, Alpert JS, et al Principles of Internal Medicine, 13th ed. New York, sympathetic tone in anaesthetized diabetics. Can J
(eds): Intensive Care Medicine. Boston, Little, McGraw-Hill, 1994, p 255. Anaesth 38:20, 1991.
Brown, 1985. 45. Drummond JC, Moore SS: The influence of dex- 67. Kannel W, McGee D: Diabetes and cardiovascular
24. Sarnaik AP, Meert K, Hackbarth R, et al: Manage- trose administration on neurologic outcome after disease: The Framingham Study. JAMA 241:2035,
ment of hyponatremic seizures in children with temporary spinal cord ischemia in the rabbit. 1979.
hypertonic saline: A safe and effective strategy. Crit Anesthesiology 70:64, 1989. 68. Haffner SM, Lehto S, Ronnemaa T, et al: Mortality
Care Med 19:758, 1991. 46. Sieber FE, Traystman RJ: Special issues: Glucose from coronary heart disease in subjects with type 2
25. Oh M, Carrol H: Disorders of sodium metabolism: and the brain. Crit Care Med 20:104, 1992. diabetes and in nondiabetic subjects with and
Hypernatremia and hyponatremia. Crit Care Med 47. Stagnaro-Green A: Perioperative glucose control: without prior myocardial infarction. N Engl J Med
20:94, 1992. Does it really matter? Mt Sinai J Med 58:299, 1991. 339:229, 1998.
26. Perez GO, Oster JR, Robertson GL: Severe hyper- 48. McMurry JF Jr: Wound healing with diabetes mel- 69. Schaade DS: Surgery and diabetes. Med Clin North
natremia with impaired thirst. Am J Nephrol 9:421, litus: Better glucose control for better wound Am 72:1531, 1988.
1989. healing in diabetes. Surg Clin North Am 64:769, 70. Gavin LA: Management of diabetes mellitus during
27. Illner HP, Cunningham JN, Shires GT: Red blood 1984. surgery. West J Med 151:525, 1989.
cell sodium content and permeability changes in 49. Welborn LG, McGill WA, Hannallah RS, et al: Peri- 71. Reissel E, Orko R, Maunuksela E, et al: Predictabil-
hemorrhagic shock. Am J Surg 143:349, 1982. operative blood glucose concentrations in pediatric ity of difficult laryngoscopy in patients with long-
28. Coran AG: Perioperative care of the pediatric outpatients. Anesthesiology 65:543, 1986. term diabetes mellitus. Anaesthesia 43:1024, 1990.
patient. Surg Ann 23(Pt 1):31, 1991. 50. Welborn LG, McGill WA, Hannallah RS, et al: 72. Hogan K, Rusty D, Springman SR: Difficult laryn-
29. Brown MJ, Brown DL, Murphy MB: Hypokalemia Glucose concentrations for routine intravenous goscopy and diabetes mellitus. Anesth Analg
from 2 receptor stimulation by circulating epine- infusion in pediatric outpatient surgery. Anesthesi- 67:1162, 1988.
phrine. N Engl J Med 309:1414, 1983. ology 67:427, 1987. 73. Davidson MB, Schriger DC, Peters AL, et al: A
30. Vincent HH, Boomsma F, Man int Veld AJ, et al: 51. Degoute CS, Ray MJ, Manchon M, et al: Intraopera- clinical approach for the diagnosis of diabetes mel-
Effects of selective and nonselective beta agonists tive glucose infusion and blood lactate: Endocrine litus: An analysis using glycosylated hemoglobin
on plasma potassium and norepinephrine. J Cardio- and metabolic relationships during abdominal levels. JAMA 276:1246, 1996.
vasc Pharmacol 6:107, 1984. aortic surgery. Anesthesiology 71:355, 1989. 74. Nathan DM: Hemoglobin A1c: Infatuation or the
31. Papademetrious V, Fletcher R, Khatri IM, et al: 52. The Carter Center of Emory University: Closing the real thing? N Engl J Med 323:1062, 1990.
Diuretic-induced hypokalemia in uncomplicated gap: The problem of diabetes mellitus in the United 75. American Hospital Formulary Service: Miscellane-
systemic hypertension: Effect of plasma potassium States. Diabetes Care 8:391, 1985. ous Antidiabetic Agents. Bethesda, MD, ASHP,
correction on cardiac arrhythmias. Am J Cardiol 53. Nesmeth J: Type 2 diabetes in children and adoles- 2000, 68.20.92 3032-41.
52:1017, 1983. cents. Pediatr Rev 105:671, 2000. 76. Glucophage R (metformin) product information.
32. Papademetrious V, Burris J, Kukish SIM, et al: 54. Foster DW: Endocrinology and metabolism. In Princeton, NJ, Bristol-Myers-Squibb, October
Effectiveness of potassium chloride or triamterene Wilson JD, Braunwald E, Fauci AS, et al (eds): Har- 2000.
in thiazide hypokalemia. Arch Intern Med 145:1986, risons Principles of Internal Medicine, 12th ed. New 77. Watson BG, Pay DA, Williamson M, et al: Practical
1985. York, McGraw-Hill, 1991, p 1743. closed-loop insulin infusion. Life Support Syst
33. DeFronzo RA: Intravenous potassium chloride 55. Engelgau MM, Herman WH, Smith PJ, et al: The 3(Suppl 1):519, 1985.
therapy. JAMA 245:2446, 1981. epidemiology of diabetes and pregnancy in the U.S., 78. Hirsch IB, Magill JB, Cryer PE, et al: Perioperative
34. Solomon RJ, Katz JD: Disturbances of potassium 1988. Diabetes Care 18:1029, 1995. management of surgical patients with diabetes mel-
homeostasis. In Stoelting RK (ed): Advances in 56. Stewart WJ, McSweeney SM, Kellet MA, et al: litus. Anesthesiology 74:346, 1991.
Anesthesia, vol 3. Chicago, Year Book Medical Pub- Increased risk of severe protamine reactions in 79. Nutt LK, ONeil RG: Effect of elevated glucose on
lishers, 1986. NPH insulin-dependent diabetics undergoing endothelin-induced store-operated and non-store-
Intravascular Fluid and Electrolyte Physiology 1737 54
operated calcium influx in renal mesangial cells. J going aortic reconstruction. Surg Gynecol Obstet patient: A critical analysis. Ann Surg 169:149,
Am Soc Nephrol 11:1225, 2000. 164:127, 1987. 1969.
80. Marhoffer W, Stein M, Maeser D, et al: Impairment 95. Rocha e Silva M, Velasco IT, Portirio MMF: Hyper- 111. Prien T, Backhaaus N, Pelster F, et al: Effect of intra-
of PMN leukocyte function and metabolic control tonic saline resuscitation: Saturated salt-dextran operative fluid administration and colloid osmotic
of diabetes. Diabetes Care 15:256, 1992. solutions are equally effective, but induce hemolysis pressure on the formation of intestinal edema
81. Furnary AP, Zerr KJ, Grunkemeier GL, Starr A: in dogs. Crit Care Med 18:203, 1990. during gastrointestinal surgery. J Clin Anesth 2:317,
Continuous intravenous insulin infusion reduces 96. Velasco IT, Pontieri V, Rocha e Silva M, et al: Hyper- 1990.
the incidence of deep sternal wound infection in osmotic NaCl and severe hemorrhagic shock. Am J 112. Schrieer RW: Pathogenesis of sodium and water
diabetic patients after cardiac surgical procedures. Physiol 239:H664-H673, 1980. retention in high-output and low-output cardiac
Ann Thorac Surg 67:352, 1999. 97. Bunn F, Roberts I, Tasker R, et al: Hypertonic versus failure, nephrotic syndrome, cirrhosis and preg-