Regulatory Mechanisms: Fluid Volume, Osmolality, and Arterial Pressure

Water is in thermodynamic equilibrium across cell membranes, and it moves only in response to the movement of solutes (E-Fig. 8-1). Movement of water is described by the Starling equation:

where Q_f is fluid flow; K_f is the membrane fluid filtration coefficient; P_c, P_i, π_c, and π_i are hydrostatic and osmotic pressures on either side of the membrane; and σ is the reflection coefficient for the solute and membrane of interest. The reflection coefficient gives a measure of a solute’s permeability and, consequently, its contribution to osmotic force after equilibration. Across the blood-brain barrier, for example, the σ for sodium approaches 1.0,¹ whereas in muscle and other cell membranes, σ is on the order of 0.15 to 0.3.² Therefore, when isotonic sodium-containing solutions are given intravenously, usually only 15% to 30% of administered salt and water remains in the intravascular space while the remainder accumulates as interstitial edema.^3,4 In contrast, hypertonic solutions permit greater expansion of circulating blood volume with smaller fluid loads and less edema.^5–7

E-FIGURE 8-1 Movement of water from the intracellular to extracellular compartments is described by the Starling equation. See text for details.

Both the amount and the concentration of solute are tightly regulated to maintain the volumes of intravascular and intracellular compartments. Because sodium is the primary extracellular solute, this ion is the focus of homeostatic mechanisms concerned with maintenance of intravascular volume. When osmolality is held constant, water movement follows sodium movement. As a result, total body sodium (although not necessarily serum Na⁺) and total body water (TBW) generally parallel one another. Because sodium “leak” across membranes limits its contribution to the support of intravascular volume, this compartment is also critically dependent on large, impermeable molecules such as proteins. In contrast to sodium, albumin molecules, for example, follow the Starling equilibrium with a reflection coefficient in excess of 0.8.⁸ Soluble proteins create the so-called colloid oncotic pressure, approximately 80% of which is contributed by albumin.

Although the presence of albumin supports intravascular volume, protein leak into the interstitium (and consequent water movement) may limit its effectiveness. It has been observed, for example, that the reflection coefficient for albumin decreases by as much as one third after mechanical trauma.⁹ Furthermore, because of ongoing leakage, a slow continuous infusion of albumen is superior to bolus administration for increasing the serum albumen concentration in critically ill individuals.¹⁰

Potassium is the primary intracellular solute, with approximately one third of cellular energy metabolism devoted to Na⁺/K⁺ exchange. Sodium continuously leaks into cells along its concentration gradient, yet it is rapidly extruded in exchange for potassium. As the cell is exposed to varying osmolarity, water movement occurs, causing cell swelling or shrinkage. Because stable cell volume is critical for survival, complex regulatory mechanisms have evolved to ensure that stability is maintained.^11,12 The processes by which swollen cells return to normal size are collectively termed regulatory volume decrease processes, and those returning a shrunken cell to normal are termed regulatory volume increase processes (Fig. 8-1). With sudden, brief changes in osmolality, regulatory volume increase or decrease processes are activated after small (1% to 2%) changes in cell volume, returning cell volume to normal primarily through transport of electrolytes. If anisosmotic conditions persist, chronic compensation occurs through the accumulation or loss of small organic molecules termed osmolytes or idiogenic osmoles (e.g., polyols, sorbitol, myoinositol), amino acids and their derivatives (e.g., taurine, alanine, proline), and methylamines (e.g., betaine, glycerylphosphorylcholine).

FIGURE 8-1 Activation of mechanisms regulating cell volume in response to volume perturbations. Volume-regulatory losses and gains of solutes are termed regulatory volume decrease (A) and regulatory volume increase (B), respectively. The course of these decreases and increases varies with the type of cell and experimental conditions. Typically, however, a regulatory volume increase mediated by the uptake of electrolytes or a regulatory volume decrease mediated by the loss of electrolytes and organic osmolytes occurs over a period of minutes. When cells that have undergone a regulatory volume decrease (A) or increase (B) are returned to normotonic conditions, they swell above or shrink below their resting volume. This is due to volume-regulatory accumulation or loss of solutes, which effectively makes the cytoplasm hypertonic or hypotonic, respectively, as compared with normotonic extracellular fluid.

(From McManus ML, Churchwell KB, Strange K. Regulation of cell volume in health and disease. N Engl J Med 1995;333:1260-6. ®Massachusetts Medical Society.)

Like intracellular volume, circulating blood (intravascular) volume is also tightly controlled. Increases in intravascular volume result from increases in sodium and water retention, whereas decreases in intravascular volume result from increases in excretion of sodium and water. As noted earlier, serum osmolality must be maintained within a very narrow range if serum sodium is to be an effective focus of intravascular volume control. Serum osmolality is usually maintained between 280 and 300 mOsm/L. Changes in osmolality as small as 1% trigger compensatory mechanisms.

Serum osmolality is primarily regulated by antidiuretic hormone (ADH), thirst, and renal concentrating ability. Because the indirect aim of osmolar control is actually volume control, these same osmoregulatory mechanisms are also influenced by factors such as blood pressure (BP), cardiac output, and vascular capacitance.^13,14 In pathologic conditions such as ascites or hemorrhage, intravascular volume preservation takes precedence over osmolality and osmoregulatory mechanisms operate to restore intravascular volume, even at the expense of disrupting physiologic solute balance.

For example, ADH is released from neurons of the supraoptic and paraventricular nuclei in response to osmolar fluctuations in cell size. Solutes that readily permeate cell membranes, such as urea, increase the serum osmolality without triggering the release of ADH. Infusion of solutes with large actual or effective reflection coefficients (σ) at the cell membrane (e.g., sodium, mannitol) elicits a robust ADH release. ADH release begins when the serum osmolality reaches a threshold of approximately 280 mOsm/L. Rapid increases in osmolality lead to a greater release of ADH than do slow increases. Hypovolemia and hypotension diminish the threshold for ADH release and increase the “gain” of the system by exaggerating the rate of increase in serum ADH concentrations (E-Fig. 8-2). Thus, in a volume-depleted or hypotensive child, brisk ADH release occurs in response to plasma osmolalities as low as 260 to 270 mOsm/L. It has been hypothesized that different populations of vasopressin-secreting cells are responsive to osmotic and baroreceptor-mediated input.

E-FIGURE 8-2 A, Relationship between plasma antidiuretic hormone (ADH) concentration and plasma osmolality in normal humans in whom the plasma osmolality was changed by varying the state of hydration. Notice that the osmotic threshold for thirst is a few milliosmols per kilogram higher than that for ADH. B, The influence of hemodynamic status on the osmoregulation of ADH in otherwise healthy humans. The numbers in the center circles refer to the percentage change in volume or pressure; N (in the center circles) refers to the normovolemic normotensive subject. Notice that the hemodynamic status affects both the slope of the relationship between the plasma ADH and osmolality and the osmotic threshold for ADH release.

(A adapted from Robertson GL, Aycinena P, Zerbe RL. Neurogenic disorders of osmoregulation. Am J Med 1982;72:339; B from Rose DB. Clinical physiology of acid-base and electrolyte disorders. 4th ed. New York: McGraw-Hill; 1994. p. 159, 163.)

Intravascular fluid volume, salt and water intake, electrolyte balance, and cardiovascular status are interrelated at several levels.¹⁵ For example, as the veins and arteries become replete with fluid and the systemic BP increases, ADH release wanes as both pressure diuresis and natriuresis commence.¹⁶ The resulting relationship between urine output and arterial pressure is termed the renal function curve, and its intersection with salt and water intake determines the equilibrium point at which arterial BP ultimately stabilizes (Fig. 8-2). Equilibrium (chronic) BP is influenced only by shifts of the renal function or fluid intake curves. Transient changes in arterial pressure secondary to peripheral vascular resistance changes are always resolved by opposing shifts in total body salt and TBW.

FIGURE 8-2 Analysis of arterial pressure regulation by equating the renal output curve with the salt and water intake curve. The equilibrium point describes the level to which the arterial pressure will be regulated. (That portion of the salt and water intake that is lost from the body through nonrenal routes is ignored in this figure.)

(From Guyton AC, Hall JC, editors. Textbook of medical physiology. Philadelphia: WB Saunders; 1996. p. 221-37.)

In response to a decreasing arterial pressure, the renin-angiotensin system is also mobilized. With decreased renal perfusion, juxtaglomerular cells release renin, which in turn converts renin substrate (angiotensinogen) to angiotensin I. Angiotensin I is then rapidly converted to angiotensin II by angiotensin-converting enzyme present in lung endothelium. Angiotensin II supports arterial pressure in three ways: (1) direct vasoconstriction, (2) increased salt and water retention (via renal vasoconstriction and decreased glomerular filtration), and (3) stimulation of aldosterone secretion (Fig. 8-3).

FIGURE 8-3 Physiologic responses to hypotension.

ADH, pressure diuresis, and the renin-angiotensin system permit wide ranges in salt and water intake without large fluctuations in BP or volume status. All serve to support the systemic circulation when threatened and complement the more immediate activity of the sympathetic nervous system. In addition to high-pressure sensors such as aortic arch and carotid sinus baroreceptors, intravascular volume information is provided by low-pressure thoracic sensors. For this reason, effective increases or decreases in intrathoracic blood volume may mimic changes in whole-body volume status and produce natriuresis, diuresis, or fluid retention. Intravascular volume may also be sensed as the stretch of atrial muscle fibers, leading to release of atrial natriuretic peptide.¹⁷ Although its complete physiologic role is uncertain, atrial natriuretic peptide may serve to “fine tune” volume status by causing modest vasodilation, gently increasing the glomerular filtration rate (GFR), and decreasing reabsorption of sodium. The combination of complex autoregulatory mechanisms with complementary actions operating on varying time scales, all responding to different, yet interrelated, effector stimuli, yields an elegant system by which the mature individual may maintain circulation amid a variety of challenges. In this context, it is interesting to observe that successful heart transplant recipients, despite general cardiovascular stability, typically manifest fundamental derangements in body fluid homeostasis.¹⁸

Maturation of Fluid Compartments and Homeostatic Mechanisms

Body Water and Electrolyte Distribution

Much of our understanding of the development of body water compartments is derived from deuterium oxide dilution studies performed in the 1950s.¹⁹ In a series of 21 neonates, TBW was found to be approximately 78 ± 5% of body weight. Subsequent measurements in fewer subjects showed that TBW decreased to approximately 60% in the second 6 months of life with most of the loss being extracellular. A smaller decrease (to about 57%) is observed late in childhood (Fig. 8-4).

FIGURE 8-4 Total body water (blue circles), extracellular water (purple triangles), and intracellular water (orange circles) as percentages of body weight in infants and children, compared with corresponding values for the fetus and adults.

(From Friis-Hansen B. Body water compartments in children: changes during growth and related changes in body composition. Pediatrics 1961;28:169-81.)

The importance of the extracellular compartment, its relationship to the intracellular space, and much of the chemical anatomy of both were first described by Gamble in educational monographs issued during the first part of the 20th century (E-Fig. 8-3).^20,21 The chemical compositions of mature body fluid compartments are provided in Table 8-1.

TABLE 8-1 Composition of Body Fluid Compartments

	Extracellular Fluid	Intracellular Fluid
Osmolality (mOsm)	290-310	290-310
Cations (mEq/L)	155	155
Na+	138-142	10
K+	4.0-4.5	110
Ca2+	4.5-5.0	—
Mg2+	3	40
Anions (mEq/L)	155	155
Cl−	103	—
HCO3−	27	—
HPO42−	—	10
SO42−	—	110
PO42−	3	—
Organic acids	6	—
Protein	16	40

E-FIGURE 8-3 Acid–base composition of body fluids. These diagrams are constructed from average values for the individual factors expressed in terms of acid–base equivalence—that is, as cubic centimeters of one-tenth normal solutions per hundred cubic centimeters of fluid. The base factors are superimposed in the left column and the acid factors are superimposed in the right column for each fluid. The diagrams represent, as is actually the case, a structure composed not of salt but of individually sustained concentrations of ions. The exact acid–base equivalence indicated by the equal height of the two columns is obtained by adjustability of the bicarbonate ion concentration (HCO₃⁻) to any change elsewhere in the structure.

(From McIver MA, Gamble JL. Body fluid changes due to upper intestinal obstruction. JAMA 1928;92:1589-92. Copyright 1928, American Medical Association.)

Fluid and Electrolyte Requirements

Holliday summarized the evolution of contemporary hydration therapy.²⁰ In 1831, Latta first reported the use of intravenous (IV) fluids in the resuscitation of patients dehydrated by cholera.²⁶ In 1918, growing information on the subject permitted Blackfan and Maxcy to successfully treat nine infants by intraperitoneal injection.²⁷ In 1923, Gamble and associates detailed the anatomy of fluid and electrolyte compartments, introducing the use of milliequivalents to clinical practice.²¹ This paved the way for the development of the “deficit therapy” regimen of Darrow.²⁸

In subsequent decades, various recipes to replace the extracellular and intracellular fluid losses were suggested. For the most part, these failed because of excessive potassium and insufficient sodium content. Hyponatremia was common. When the focus of the treatment shifted to replacing the extracellular fluid deficit, rapid restoration of extracellular fluid volume using solutions with sodium concentrations similar to those in blood became commonplace. This, along with oral rehydration, is the preferred method of treatment today.

The concept of “maintenance fluids” is a complex subject. Although water and salt are required to sustain life, it is fair to say that for an individual child at any particular time, the precise amounts necessary are unknown (and perhaps unknowable). Instead, fluids and electrolytes, like anesthetics, are titrated to effect with general guidelines provided by clinical assessment, basic physiologic principles, and limited published data. The term maintenance fluids is often more limiting than helpful, and in all cases it is less precise than other terms familiar to anesthesiologists, such as minimal alveolar concentration (MAC) or median effective dose (ED₅₀).

Holliday and Segar provided calculations for a first approximation of “the maintenance need for water in parenteral fluid therapy” in 1957.²⁹ Integrating the relevant known physiology at that time, these authors observed that “insensible loss of water and urinary water loss roughly parallel energy metabolism and do not parallel weight.” However, because water utilization parallels energy metabolism, energy metabolism follows surface area, and surface area follows weight, it should be possible to estimate water requirement from weight alone. The authors then proceeded under a series of assumptions to extrapolate from limited data to a “relationship between weight and energy expenditure that might easily be remembered.”

Assuming energy requirements of “hospitalized patients” to be “roughly midway between basal and normal levels,” they constructed a curve of caloric requirement versus weight.²⁹ This curve could be seen as comprising three linear sections: 0 to 10 kg, 10 to 20 kg, and 20 to 70 kg (Fig. 8-5). Viewing the curve in this manner, the authors reasoned that “fortuitously, the average need for water, expressed in milliliters, equals energy expenditure in calories”: 100 mL/kg/day for weights to 10 kg, an additional 50 mL/kg/day for each kilogram from 11 to 20 kg, and 20 mL/kg/day more for each kilogram beyond 20 kg. In anesthetic practice, this formula has been further simplified, with the hourly requirement referred to as the “4-2-1 rule” (4 mL/kg/hr for the first 10 kg of weight, 2 mL/kg/hr for the next 10 kg, and 1 mL/kg/hr for each kilogram thereafter; Table 8-3).

FIGURE 8-5 The upper and lower curves were plotted from data from the study by Talbot.¹²⁶ Weights at the 50th percentile level were selected for converting calories at various ages to calories related to weight. The computed line for the average hospitalized child was derived from the following equations:

1. 0-10 kg: 100 kcal/kg.

2. 10-20 kg: 1000 kcal + 50 kcal/kg for each kg over 10 kg

3. 20 kg and up: 1500 kcal + 20 kcal/kg for each kg over 20 kg

(From Holliday MA, Segar WE. The maintenance need for water in parenteral fluid therapy. Pediatrics 1957;19:823-32.)

TABLE 8-3 Relationship between Weight and Hourly or Daily Maintenance Fluid Requirements of Children as per the 4-2-1 Rule

For decades, the simplicity and elegance of the Holliday and Segar formula has made it the starting point for fluid management in healthy children. As recently as 2006, the majority of consultant anesthetists in the United Kingdom administered hyponatremic glucose-containing solutions intraoperatively and postoperatively to children undergoing elective surgery.³⁰ However, the uncritical use of these solutions was never intended, and their blind application in the operating room, or in any clinical situation, is unwarranted. Further, as Holliday and Segar have themselves pointed out, their original approach involved hyponatremic glucose-containing solutions rather than near-isotonic solutions such as 0.9% saline or lactated Ringer solution (LR).^30a In addition, these requirements were assessed at a basal metabolic state and not when the child was acutely ill or under physiologic stress. As the authors cautioned that “understanding of the limitations and of exceptions to the system [is] required. Even more essential is the clinical judgment to modify the system as circumstances dictate.” General water losses for infants and children are summarized in Table 8-4.

TABLE 8-4 Normal Water Losses for Infants and Children

More recently, Holliday revised the approach to fluid therapy in children that he and Segar enshrined with several caveats.^30b In a related commentary, Holliday pointed out several problems with applying the original 4-2-1 rule to acutely ill children.^30c Namely, dysregulation of ADH is a hallmark of critical illness because ADH secretion is affected by a variety of nonosmotic factors such as pain, stress, mechanical ventilation, and many medications. As a result, the choice of intravenous fluid and the rapidity of deficit replacement must be approached with care. The authors recommended a relatively simple strategy for healthy children undergoing elective surgery (including outpatients) to turn off ADH secretion and prevent perioperative water retention and subsequent hyponatremia. When a child (who is without significant heart or kidney disease) presents with marginal to moderate hypovolemia (e.g., after fasting for surgery), 20 to 40 mL/kg of isotonic fluids should be given during surgery and the postanesthesia care unit stay (as rapidly as 10 to 20 mL/kg/hr). Clinical judgment must always allow for modification of these recommendations if indicated for an individual child.^31,32 If hypovolemia is more severe (e.g., after an extensive bowel preparation), 40 to 80 mL/kg may be necessary during the perioperative period.

Postrecovery IV fluid therapy should consist of an isotonic solution infused at half the rate described in the original 4-2-1 fluid regimen (i.e., 2 mL/kg for the first 10 kg, 1 mL/kg for the next 10 kg, and 0.5 mL/kg for each additional kilogram thereafter). If the child does not or cannot tolerate oral intake after 6 to 12 hours, standard maintenance fluid therapy using hypotonic saline (e.g., 0.45% saline) should be initiated to avoid hypernatremia and fluid overload from prolonged administration of the isotonic solutions. This regimen should limit the ADH response and reduce the risk for postoperative hyponatremia and hypernatremia.^31–33 It remains essential, however, to monitor plasma electrolyte concentrations serially on the ward, regardless of the fluid doctrine followed, to be certain that electrolyte concentrations remain within normal limits.^34,35

Intraoperative Fluid Management

Intravenous Access and Fluid Administration Devices

In pediatrics, the first step toward intraoperative fluid management is often the most challenging: that is, gaining IV access. In general, simple procedures in healthy children are successfully approached using a single peripheral IV line. Although preferences vary among anesthesiologists, establishing IV access is most easily accomplished after induction of anesthesia. In young children, anesthesia is often induced by inhalation, and a catheter is inserted by an assistant into a hand or foot vein. In older children, or when IV access is desirable before anesthesia is induced, IV access may be facilitated by the use of topical anesthesia (e.g., EMLA cream, amethocaine, lidocaine infiltration) or sedation or both.

Complex surgeries in sicker children usually require at least two large-bore catheters. In pediatrics, however, “large bore” is a relative term, with 22-gauge catheters typically providing sufficient access in infants. Preferred sites for larger catheters include the antecubital and saphenous veins. In cases in which access to the central circulation is required (as for pressure monitoring, infusion of vasoactive medications, or prolonged access), longer catheters may be placed via the femoral, subclavian, or internal jugular vein (the latter usually via a high, anterior approach).⁴⁰ Although secure access may also be obtained via the external jugular vein, it is often difficult to negotiate the J-wire or catheter tip into the central circulation.⁴¹ Peripherally inserted central catheter (PICC) lines are becoming increasingly used in hospitalized children. Although they represent a long-term means of delivering IV fluids and medications in children who require such treatment interventions, there are limitations to their utility intraoperatively. First, practitioners must maintain strict sterile technique when accessing these lines in order to avoid infection. Second, the lines tend to have smaller diameters and are quite long. Therefore, resistance can be significant, even with larger-bore PICC lines. Consequently, bolus and infusion dosing of drugs can be met with high resistance. These lines are not appropriate for large-volume resuscitation, and care should be taken to secure larger-bore IV access if large fluid shifts or significant blood loss is anticipated.

In selecting the appropriate IV catheter, it is useful to consider the relative effects of catheter length and diameter on solution flow rates. Longer catheters offer more resistance to flow than shorter ones and are therefore less desirable when rapid infusion of a large volume of fluids is necessary (see E-Fig. 51-1 and Figs. 51-1, 51-2). In vitro, catheters that were designed for peripheral venous access had 18% to 164% greater flow rates when compared with the same-gauge catheters designed for central venous use. Under pressure, as might be employed during emergent volume resuscitation, rates differed up to 17-fold.⁴² Although this seems to suggest that short peripheral catheters should be preferred, in vivo data are more complex. In animal models, overall catheter flow rates are less than in vitro rates, and central access presents somewhat less resistance to flow than peripheral access.⁴³ Finally, when weighing the risks and benefits of central versus peripheral access, it is also interesting to consider that central administration of resuscitation medications may provide little practical advantage over peripheral administration.⁴⁴

Intraosseous devices are now commonly used in the initial resuscitation of critically ill or injured children (see Fig. 48-6).^45,46

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

Perioperative Behavioral Stress in Children Total Intravenous Anesthesia and Target-Controlled Infusion Medicolegal Issues Organ Transplantation Burn Injuries Ultrasound-Guided Regional Anesthesia

Stay updated, free articles. Join our Telegram channel

Join