8 Fluid Management
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 Qf is fluid flow; Kf is the membrane fluid filtration coefficient; Pc, Pi, πc, and πi 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
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).
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.
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.
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).
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).
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.
| 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 |
Circulating Blood Volume
The blood volume in neonates was determined to be 82 ± 9 mL/kg using an iodine 121–labeled human serum albumin technique, although substantial variability may result from the degree of placental-fetal transfusion.22 In low-birth-weight (LBW), preterm, or critically ill infants, values as high as 100 mL/kg have been measured.23 Blood volume increases slightly during the first few months of life, reaching its zenith at 2 months of age (approximately 86 mL/kg), then returns to near 80 mL/kg and finally stabilizes at 70 mL/kg by the end of the first year of life. In general, the ratio of blood volume to weight decreases with growth. The most accurate basis for prediction of blood volume is lean body mass, the consideration of which removes any male/female variation even into adulthood.24 An estimate of the circulating blood volume is presented in Table 8-2.
| Age | Estimated Blood Volume (mL/kg) |
|---|---|
| Preterm infant | 100 |
| Full-term neonate | 90 |
| Infant | 80 |
| School age | 75 |
| Adults | 70 |
Maturation of Homeostatic Mechanisms
In the first year of life, renal plasma flow and GFR are approximately one half the adult values of 350 and 70 mL/min/m2, respectively.25 Consequently, serum creatinine is increased in term and preterm infants, yet normalizes in the second month of life. Fractional excretion of sodium (FENa) is markedly increased in preterm infants, decreases somewhat by term, and stabilizes at adult levels by the second month of life. Although the adult kidney may easily achieve FENa values as low as 0.5%, the 34-week-gestation infant is limited to no less than 2%.
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
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:
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
| MAINTENANCE FLUID REQUIREMENTS | ||
|---|---|---|
| Weight (kg) | Hour | Day |
| <10 | 4 mL/kg | 100 mL/kg |
| 10-20 | 40 mL + 2 mL/kg for every kg >10 kg | 1000 mL + 50 mL/kg for every kg >10 kg |
| >20 | 60 mL + 1 mL/kg for every kg >20 kg | 1500 mL + 20 mL/kg for every kg >20 kg |
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
| Cause of Loss | Volume of Loss (mL/100 kcal) |
|---|---|
| Output | |
| Urine | 70 |
| Insensible loss | |
| Skin | 30 |
| Respiratory tract | 15 |
| Hidden intake (from burning 100 calories) | 15 |
| Total | 100 |
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
Neonatal Fluid Management
Three distinct phases of fluid and electrolyte homeostasis have been described in LBW36 and very low–birth-weight (VLBW)37 infants. In the first day of life, there is minimal urine output, and body weight is stable despite low fluid intake. In the second phase, days 2 and 3 of life, diuresis occurs irrespective of the amount of fluid administered. By the fourth and fifth days of life, urine output begins to vary with changes in fluid intake and state of health.
In the neonatal ICU, fluid management focuses on provision of adequate nutrition, maintenance of electrolyte balance, and limitation of fluid overload. The last factor is of particular concern because plasma oncotic pressure is reduced in preterm infants and the whole-body protein reflection coefficient is less than that in adults.38 VLBW infants are at particular risk for fluid and electrolyte imbalances.39 Even modest fluid overload may exacerbate pulmonary edema, prolong ductal patency, and more readily produce congestive heart failure. This perspective typically accompanies the infant to the operating room, where the primary considerations are routinely quite the opposite: restoration of circulating blood volume after third space accumulation, maintenance of intravascular volume amid ongoing blood loss, replacement of potentially massive evaporative losses, and maintenance of BP despite anesthetic-induced vasodilatation and increased venous capacitance. During surgery, these concerns must take precedence; yet unnecessary administration of fluid is best avoided.
Intraoperative Fluid Management
Intravenous Access and Fluid Administration Devices
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
