Core Curriculum in Nephrology

Fluid Management in Adults and Children: Core Curriculum 2014

Danielle Davison, MD,1,2 Rajit K. Basu, MD,3,4 Stuart L. Goldstein, MD,3 andLakhmir S. Chawla, MD1,2

BACKGROUND: PHYSIOLOGY

Overview

An understanding of fluid compartments, includingthe structure and function of the cell and capillarymembranes and the changes that occur in health andin disease, is key to providing appropriate fluidmanagement. The effective circulating volume is thepart of the extracellular fluid that maintains perfusionto tissues. The cornerstone of volume management isto maintain the effective circulating volume to opti-mize oxygen delivery to tissues early in the diseaseprocess while avoiding interstitial edema. Havingknowledge of the physiologic principles that deter-mine volume distribution—in other words, knowingwhat happens to the fluid after a volume challenge hasbeen given—can influence the type and amount offluid administered.

Intracellular Versus Extracellular Compartments

In adults, total-body water (TBW) comprisesw60% of lean body weight and therefore is the mostabundant component in the human body. This variesbased on sex (TBW comprises a higher percentage oflean body weight in males than in females) and age(the percentage decreases with age). The variation inwater weight is due largely to the amount of adiposetissue in the body, which holds significantly lesswater than muscle. TBW is divided into the extra-cellular and intracellular fluid compartments. Thedistribution of water can be remembered by the “two-thirds/one-third and three-fourths/one-fourth” conceptillustrated in Fig 1. There is considerable variation inTBW in children. Neonates, infants, and childrencarry a significantly higher percentage of TBW

From the Divisions of 1Anesthesiology and 2Critical Care,George Washington Medical Center, Washington, DC; 3Divisionof Critical Care, and 4Department of Pediatrics, Center for AcuteCare Nephrology, Cincinnati Children’s Hospital and MedicalCenter, University of Cincinnati, Cincinnati, OH.Received July 9, 2013. Accepted in revised form October 15,

2013. Originally published online December 13, 2013.Address correspondence to Lakhmir S. Chawla, MD, Depart-

ment of Anesthesiology and Critical Care Medicine and Divisionof Renal Diseases and Hypertension, Department of Medicine,George Washington University Medical Center, 900 23rd St, NW,Washington, DC. E-mail: minkchawla@gmail.com� 2014 by the National Kidney Foundation, Inc.0272-6386/$36.00http://dx.doi.org/10.1053/j.ajkd.2013.10.044

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compared with adults due to reduced fat content andincreased muscle mass proportion. TBW percentagegradually decreases by toddler age (Fig 1B), mirroredby the increase in intracellular fluid volume secondarynot only to muscle growth, but also to decreasingrates of collagen production.

Osmolality, Vascular Barrier, and Integrity

Osmotic forces are the main determinant of waterdistribution and movement throughout the body.Solutes that cannot freely cross the cell membraneexert osmotic pressure on that compartment, resultingin fluid shifts across the membrane. Because waterfreely crosses almost all cell membranes, a change inosmolality in one compartment will trigger watermovement across the cell membrane to the side withhigher osmolality. This specifically describes theforces that occur between the intracellular and extra-cellular compartments across cell membranes. Thecalculation for serum osmolality is: 2 3 [Na1] 1[urea nitrogen]/2.8 1 [glucose]/18. It is important tonote that while this calculation includes glucose andserum urea nitrogen, both these substances permeatereadily across most cell membranes and are ineff-ective osmoles. Therefore, the most abundant extra-cellular cation, sodium, greatly affects waterhomeostasis. Control over serum osmolality is main-tained by the intricate feedback loop between thehypothalamus and the juxtaglomerular apparatus inthe kidney. Release of arginine vasopressin secondaryto hyperosmolarity detected by osmoreceptors in theanteroventral hypothalamus leads to upregulation ofaquaporin channels in the collecting duct of the kid-ney. Simultaneously, osmoreceptors in the juxtaglo-merular apparatus detect changes in solute (ie,sodium) delivery and volume status and regulate therenin-angiotensin-aldosterone axis to change fluid andsodium retention in renal tubules. In periods of vol-ume imbalance, the 2 osmoreceptor mechanisms workin tandem with each other and with the sympatheticnervous system to regulate a precise balance of so-dium and extracellular water volume (Fig 2). In smallchildren, susceptibility to volume depletion isincreased secondary to immature hypothalamicosmoreceptor function and inadequately developedjuxtaglomerular apparatus signaling. Additionally, thehigher percentage of their body weight in TBW placessmall children at greater risk of more significant he-modynamic compromise in situations of volumedepletion.

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Figure 1. (A) Fluid compartments within the human body. (B) Total-body water (TBW) content by age.

Fluid Management in Adults and Children

The intravascular and interstitial compartmentsare separated by capillary membranes, and themechanism of fluid shift differs from that described,where capillaries and small postcapillary venules actas the sites of exchange. In 1896, Ernest Starlingdescribed the classic model of vascular barrierfunction, specifically that net filtration betweenplasma and interstitium is determined by physicalfactors, including hydrostatic pressure, oncoticpressure, and the permeability of the barrier sepa-rating the 2. The Starling principle declared that thevascular barrier function is the sole responsibility ofthe single endothelial cell line. However, morerecent data suggest that the healthy endotheliallining is coated with another barrier called theglycocalyx. The glycocalyx is w1 mm in thicknessand binds proteins, thereby increasing oncoticpressure within the endothelial surface layer and

Figure 2. Volume and osmolality ho-meostasis. Abbreviations: AVP, argininevasopressin; GFR, glomerular filtrationrate; JGA, juxtaglomerular apparatus;SNS, sympathetic nervous system.

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further preventing an egress of fluid into the inter-stitium. In addition, a free space containing minimaloncotic pressure resides just adjacent to the glyco-calyx and endothelial layers. A pressure gradientbetween the glycocalyx and free space is generated,which further reduces fluid shifts across thevascular wall. Thus, the glycocalyx, along with theadjacent endothelial cell layer, forms this doublebarrier to prevent tissue edema.Any form of disruption to the glycocalyx can

result in increased transendothelial permeability andultimately in interstitial edema. Tumor necrosis fac-tor a (TNF-a) and other cytokines, known to beindicative of systemic inflammation, have beenshown to be associated with a decrease in thethickness and breakdown of the glycocalyx, leadingto increased vascular permeability. Similar cases ofglycocalyx degradation and increased vascular

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Table 1. Crystalloid Solutions

Na1

(mEq/L)

K1

(mEq/L)

Ca11

(mEq/L)

Mg11

(mEq/L)

Cl2

(mEq/L) Buffers (mEq/L electrolyte)

Glucose

(g/L) pH

POsm

(mOsm/L)

Plasma 141 4.5 5 2 103 Bicarbonate, 26; protein, 16 0.7-1.1 7.4 290

Isotonic

Normal

saline

154 — — — 154 — — 6.0 308

Lactated

Ringer’s

solution

130 4 4 — 109 Lactate, 28 — 6.5 274

Plasma-Lyte 140 5 — 3 98 Acetate, 27; Glucose, 23 — 7.4 294

Hypotonic

D5W — — — — — — 50 4.5 252

D5W1/2 NS 77 — — — 77 — 50 5.0 406

Hypertonic

7.5% NaCl 1,284 — — — 1,284 — — 6.0 2,568

Abbreviations: Ca11, calcium ion; Cl2, chloride ion; D5W, 5% dextrose; D5W1/2 NS, 5% dextrose in half-normal saline; K1, po-

tassium ion; Mg11, magnesium ion; Na1, sodium ion; NaCl, sodium chloride; POsm, plasma osmolality.

Davison et al

permeability have occurred after ischemia-reperfusioninjury. Finally, the release of atrial natriuretic peptidesecondary to excessive volume resuscitation can causedamage to the double barrier, further exacerbatingtissue edema.

Additional Readings

» Chappell D, Jacob M, Becker BF, Hofmann-Kiefer K,Conzen P, Rehm M. Expedition glycocalyx. A newlydiscovered “great barrier reef.” Anaesthesist. 2008;57(10):959-969.

» Chappell D, Westphal M, Jacob M. The impact of the gly-cocalyx on microcirculatory oxygen distribution in criticalillness. Curr Opin Anaesthesiol. 2009;22(2):155-162.

» Klinger JR, Tsai SW, Green S, Grinnell KL, Machan JT,Harrinton EO. Atrial natriuretic peptide attenuates agonist-induced pulmonary edema in mice with targeted disruptionof the gene for natriuretic peptide receptor-A. J Appl Physiol.2013;114(3):307-315.

» Ranadive SA, Rosenthal SM. Pediatric disorders of waterbalance. Pediatr Clin North Am. 2011;58(5):1271-1280.

» Rhem M, Zahler S, Lötsch M, et al. Endothelial glycocalyxas an additional barrier determining extravasation of 6%hydroxyethyl starch or 5% albumin solutions in the coronaryvascular bed. Anesthesiology. 2004;100(5):1211-1223.

» Singh A, Satchell SC. Microalbuminuria: causes and impli-cations. Pediatr Nephrol. 2011;26(11):1957-1965.

» Strunden MS, Heckel K, Goetz AE, Reuter DA. Perioperativefluid and volume management: physiologic basis, tools andstrategies. Ann Intensive Care. 2011;1(1):2.

FLUID TYPES

Overview

Since the first infusion of intravenous fluid in1832 during the cholera epidemic to present day,when fluids are the most frequently prescribed ther-apy in the intensive care unit (ICU), the quest for the“best” solution has been a subject of ongoing debateand inquiry.

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Crystalloid Solutions

Crystalloids are aqueous solutions of inorganic andsmall organic molecules and are either hypotonic,isotonic, or hypertonic with respect to plasma.Isotonic crystalloids distribute freely across thevascular barrier; approximately one-fourth of the so-lution stays within the vascular space, assuming anintact vascular barrier. Clinically, this translates to a1-L sodium chloride (NaCl) solution bolus resultingin a 250-mL expansion of circulating volume.Therefore, large volumes of crystalloids often areneeded to maintain intravascular volume, potentiallyat the cost of generating interstitial edema. Hypertonicsolutions, such as 3% or 7.5% NaCl, often are used inthe treatment of severe hyponatremia. Many haveadvocated for the use of hypertonic saline solution torestore intravascular volume rapidly; however, datado not support its use as a resuscitation strategy.Similarly, hypotonic fluid (ie, half-normal saline so-lution) is used for treating hypernatremia or free waterdeficit, but is not an effective resuscitative fluid.In addition to tonicity, crystalloids can be defined

by their electrolyte makeup. Balanced solutionscontain a physiologic mixture of electrolytes andbuffers in an effort to replicate the makeup of plasma.Examples include lactated Ringer’s solution, Isolyte(B. Braun Medical Inc), and Plasma-Lyte (Baxter).Unbalanced solutions do not contain extra electrolytesor addition of a buffer. NaCl solution is the typicalunbalanced solution. A summary of the variouscrystalloid solutions can be found in Table 1. Foryears, internal medicine specialists have favored theuse of NaCl solution as a resuscitation fluid due toconcerns that electrolytes added to balanced solutionmight be harmful in patients with kidney impairmentwho cannot handle, for example, a potassium load.

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Fluid Management in Adults and Children

However, large-volume resuscitation with NaCl so-lution results in hyperchloremic metabolic acidosis,which now has been shown to have deleterious con-sequences. In studies of both animals and humans,excess extracellular chloride is associated withincreased afferent arteriolar resistance and subsequentreduced cortical perfusion and diminished glomerularfiltration rate. In a surgical study of open-abdomenpatients that compared 0.9% NaCl to Plasma-Lytesolution, major complications, including anincreased risk of patients requiring renal replacementtherapy (RRT), was observed in the chloride-liberalgroup. A large prospective sequential-period pilotstudy compared a chloride-liberal approach versus achloride-restricted regimen through patients’ entireICU stays. Results demonstrated an increased inci-dence of acute kidney injury (AKI) and RRT in thechloride-liberal group.Due to concerns about the ability of neonatal and

infant kidneys to handle high-solute load, hypotonicresuscitative fluids traditionally have been used forrestoring adequate circulating effective volume.However, high incidences of hyponatremia and hy-poglycemia warranted investigation and comparisonwith other crystalloid solutions. Isotonic salt solutionand isotonic salt solution with dextrose have beendemonstrated to reduce the number of electrolyte im-balances (primarily hyponatremia and hypoglycemia)in resuscitation in children. The recent FEAST (FluidExpansion as Supportive Therapy) Study receivedworldwide attention by examining resuscitation ofmore than 1,000 Kenyan, Tanzanian, and Ugandanchildren presenting with severe infection (w60%malaria) using either normal saline solution bolus,albumin bolus, or no bolus and reported increasedmortality in children receiving fluid boluses versus nobolus. Importantly, the cause of death in patients whoreceived the 20- to 40-mL/kg bolus fluids could not belinked to hypernatremia, hyperchloremia, edema, orany direct effect from resuscitative fluids. Unfortu-nately, randomized data regarding the use of morebalanced salt solutions (ie, Plasma-Lyte) versus puresalt solution are unavailable.Given the body of evidence, the authors of this

review recommend the use of balanced over unbal-anced crystalloid solutions. However, certain clinicalscenarios require individual consideration. Patientswith cerebral edema or traumatic brain injury cannottolerate even relatively hypotonic solutions due to therisk of cellular swelling. Therefore, lactated Ringer’ssolution, by the nature of its low sodium content, iscontraindicated in these patients. In patients at risk ofcerebral swelling, we recommend a balanced isotonicsolution when resuscitation is necessary. Balancedsolutions also should be avoided in patients withalkalemia or severe hyperkalemia. Last, use of

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lactated Ringer’s solution requires intact liver func-tion to convert lactate into bicarbonate and thereforeis not recommended in patients with significant liverdysfunction. In children, there currently is not enoughevidence to support routine use of balanced salt so-lutions over unbalanced salt solutions, though purephysiologic data obtained from animal models indi-cate that unbalanced solutions could be even moredetrimental to children than they are to adults.

Colloid Solutions

Colloids are homogenous noncrystalline substancesthat contain large molecules. In theory, colloids havea greater capacity to remain within the intravascularspace and therefore restore hemodynamics withsmaller quantities of volume infused. Colloids inclinical practice include human plasma derivatives(albumin, fresh frozen plasma, and blood) and semi-synthetic colloids (starches, gelatin, and dextran).Albumin has been used for resuscitating hemody-namically unstable patients for decades. It achievedits greatest popularity after its use in Pearl Harborvictims, in which resuscitative goals were achievedefficiently. Albumin is the most costly of colloid so-lutions and, as a human body product, contains a verysmall risk of infectious transmission. It is available in5% (50-g/L) and 25% (250-g/L) solutions and mostoften is given in a 250-mL followed by a 50-mLvolume. Certain religious groups (eg, Jehovah’sWitnesses) forbid its use. Hydroxyethyl starches(HESs) are the most widely used semisyntheticresuscitation fluids. Examples include Volulyte (Fre-senius Kabi), Hespan (B. Braun Medical Inc), andVoluven (Hospira). HESs are described by theiraverage molecular weight (130-200 kDa) and degreeof molar substitution (ie, the proportion of glucoseunits on the starch molecule replaced by hydroxyethylunits; typically 0.35-0.5). An HES is described furtherby its concentration in percent (ie, grams per100 mL). For example, 6% HES 130/0.4 contains 6%solution of 130-kDa molecules with 0.4% of theglucose molecules substituted. HESs have a lowercost per unit compared to albumin. Dextrans are high-molecular-weight D-glucose polymers that are bio-synthesized commercially from sucrose. They aredescribed by average molecular weight: dextran 40and dextran 70. Dextrans are rarely used in adults.Gelatins are prepared by hydrolysis of bovinecollagen. Due to concerns about coagulopathy andbleeding, gelatins were withdrawn from the market inthe United States in 1978.

Crystalloid Versus Colloid Solutions: The Data

Despite decades of inquiry and study, there has yetto be a large randomized controlled trial to demon-strate that one type of fluid is superior to the other.

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Colloid supporters focus on the large volume of crys-talloid needed to achieve intravascular resuscitationgoals. Those who favor crystalloids point to the po-tential side effects of colloids, including hematologicderangement and adverse drug reaction, as well as thehigher cost. As stated, under healthy conditions, col-loids are too large to permit passage across the capillarymembrane and thus restore circulating volume effi-ciently. However, in the setting of inflammatory con-ditions and vascular barrier breakdown, the distributionof colloids looks very similar to that of crystalloidsbecause both migrate from the vascular compartmentinto the interstitial space. This physiologic principlelikely is the reason that few studies can demonstratesuperiority of one fluid over the other.

Albumin Versus Crystalloids

As the primary determinant of oncotic pressure anddriver of fluid distribution between compartments inthe human body, albumin has great appeal as aresuscitative fluid. Albumin was a staple for volumeresuscitation until a meta-analysis in 1998 showed thatit was associated with increased mortality. Opinionschanged again after publication of the SAFE (SalineVersus Albumin Fluid Evaluation) trial in 2005 inwhich survival, number of days spent in the ICU andhospital, and days spent on mechanical ventilationafter receiving 4% albumin versus 0.9% NaCl solutionwere shown to be similar. Subsequent trials havedemonstrated albumin’s safety. In a SAFE subgroupanalysis, patients with severe head injury had worseoutcomes when treated with albumin, whereas patientswith severe sepsis showed some degree of improve-ment with albumin compared with saline. Albuminshould not be given to patients with traumatic braininjury for this reason. Albumin is indicated in spon-taneous bacterial peritonitis as another trial demon-strated a benefit of albumin to survival of cirrhoticpatients with the condition. Finally, in dialysis patientswho require large-volume ultrafiltration, a 250-mLbolus of 5% albumin can be invaluable in order tomaintain mean arterial pressure. In several smallstudies, primarily limited to patients with malaria anddengue fever in resource-poor areas, albumin appearedto be associated with lower overall mortality than sa-line solution when used as fluid of choice for resus-citating critically ill children. Unfortunately, there areno current controlled studies examining colloid versuscrystalloid resuscitation in children with sepsis or se-vere hypovolemia in developed nations.

Starch Versus Crystalloids

HESs have been under increasing scrutiny in recentyears. In 2008, the VISEP (Efficacy of VolumeSubstitution and Insulin Therapy in Severe Sepsis)trial showed that patients who received 10%

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pentastarch (HES 200/0.5) solution were twice aslikely to develop AKI and trended toward increasedmortality. Subsequent trials, including 6S (Scandina-vian Start for Severe Sepsis/Septic Shock) andCHEST (Crystalloid Versus Hydroxyethyl StarchTrial), compared lower weight HES with crystalloidsolutions and again showed an association betweenHES exposure and the need for RRT. As a result ofthese findings, a European task force on colloidtherapy recommends that starch solutions not be usedoutside the context of clinical trials. The presentSurviving Sepsis Campaign states that fluid resusci-tation should begin with crystalloid, albumin shouldbe considered in patients who continue to requiresubstantial amounts of crystalloid, and HES should beavoided. Combining the available evidence, guide-lines, and costs, we favor the use of balanced crys-talloid solution with sparing use of albumin for theconditions outlined.Though less expansive, results from studies in

children comparing unbalanced to balanced electro-lyte solutions mirror data obtained from adult studies.For example, comparison of HES (HES 130/0.42/6:1)in normal saline solution (ns-HES) to balanced saltsolution (bal-HES) for perioperative resuscitationdemonstrated a significantly higher incidence ofhyperchloremia in the ns-HES group and improvedsafety for bal-HES use in neonates and small infants.

Additional Readings

» Akech S, Lederman H, Maitland K. Choice of fluids forresuscitation in children with severe infection and shock:systematic review. BMJ. 2010;341:c4416.

» Bayer O, Reinhart K, Kohl M, et al. Effects of fluid resus-citation with synthetic colloids or crystalloids alone onshock reversal, fluid balance, and patient outcomes in pa-tients with severe sepsis: a prospective sequential analysis.Crit Care Med. 2012;40(9):2543-2551.

» Brunkhorst FM, Engel C, Bloos F, et al; German CompetenceNetwork Sepsis (SepNet). Intensive insulin therapy andpentastarch resuscitation in severe sepsis. N Engl J Med.2008;358(2):125-139.

» Cochrane Injuries GroupAlbuminReviewers. Human albuminadministration in critically ill patients: systematic review ofrandomized controlled trials. BMJ. 1998;317(7153):235-240.

» Chowdhury AH, Cox EF, Francis ST, Lobo DN. A random-ized, controlled, double-blind crossover study on the effects of2-L infusions of 0.9% saline and Plasma-Lyte R 148 on renalblood flow velocity and renal cortical tissue perfusion inhealthy volunteers. Ann Surg. 2012;256(1):18-24.

» Legrand M. Fluid resuscitation does not improve renaloxygenation during hemorrhagic shock in rats. Anesthesi-ology. 2010:112(1):119-127.

» Maitland K, Kiguli S, Opoka RO, et al; on behalf of theFEAST Trial Group. Mortality after fluid bolus in Africanchildren with severe infection. N Engl J Med.2011;364(26):2483-2495.

» Myburgh JA, Finfer S, Bellomo R, et al; CHESTInvestigators. Hydroxyethyl starch or saline for fluidresuscitation in intensive care. N Engl J Med. 2012,367(20):1901-1911.

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Fluid Management in Adults and Children

» SAFE Study Investigators. A comparison of albumin andsaline for fluid resuscitation in the intensive care unit. N EnglJ Med. 2004;350(22):2247-2256.

» Shaw AD, Bagshaw SM, Goldstein SL, et al. Major com-plications, mortality, and resource utilization after openabdominal surgery: 0.9% saline compared to Plasma-Lyte.Ann Surg. 2012;255(5):821-829.

» Sort P, Navasa M, Arroyo V, et al. Effect of intravenousalbumin on renal impairment and mortality in patients withcirrhosis and spontaneous bacterial peritonitis. N Engl J Med.1999;341(6):403-409.

» Sumpelmann R, Witt L, Brutt M, Osterkorn D, Koppert W,Osthaus WA. Changes in acid-base, electrolyte and hemo-globin concentrations during infusion of hydroxyethyl starch130/0.42/6:1 in normal saline or in balanced electrolytesolution in children. Paediatr Anesthesth. 2010;20(1):100-104.

» The 6S Trial Group and the Scandinavian Critical Care TrialsGroup; Perner A, Haase N, Guttormsen AB, et al. Hydrox-yethyl starch 130/0.42 versus Ringer’s acetate in severesepsis. N Engl J Med. 2012;367(2):124-134.

» Yunos MM, Bellomo R, Hegarty C, Story D, Ho L, BaileyM. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy andkidney injury in critically ill adults. JAMA. 2012;308(15):1566-1572.

FLUID MANAGEMENT

Targets of Fluid Resuscitation

Securing adequate intravascular volume andensuring optimal perfusion is the primary goal ofresuscitation in critical care management. The studyby Rivers et al demonstrated that early resuscitationusing a goal-directed algorithmic approach improvedsurvival. Although this study has not been validatedin a multicentered randomized trial (currently inprogress) and many aspects of an early goal-directedtherapy protocol have been contested, the impor-tance of recognizing inadequate tissue perfusion andoxygen debt early is emphasized by this study’sfindings. The time-honored method of assessment isbased on physical findings, including tachycardia,hypotension, dry mucous membranes, altered menta-tion, and decreased urine output, are not reliable in-dicators of intravascular volume. Hypotension is alate indicator of shock and reflects failure ofcompensation or volume loss . 20%. Hypotensionalso may reflect pure vasodilation (eg, a side effect ofanesthesia) and not volume depletion. In the trial byRivers et al, average mean arterial pressure in theearly goal-directed therapy group was 76 mm Hg,while the control group’s was 76 mm Hg, and yetlactate values were . 4 mEq/L, indicating hemody-namic compromise. Urine output is not a reliable in-dicator either, especially in a setting in which renalblood flow alone may not be the cause for oliguria, forexample, sepsis-induced AKI.The primary target of resuscitation in children may

simply be timely resuscitation. Unfortunately, volume

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correction in children offers several unique challengesthat are not present in adults. Robust data, startingwith a landmark study by Carcillo et al demonstratinga marked improvement in survival in patients withseptic shock who received 40 mL/kg of fluid in thefirst hour versus those who did not, support institutingearly and rapid correction of volume deficit in chil-dren. More recent retrospective studies published inthe past 3-5 years support the use of early and rapidinfusion of fluids. Unfortunately, rapid infusion offluids in children often is easier said than done.Catheter properties limit the speed of fluid deliverysecondary to Poiseuille’s law, which states thatresistance is inversely proportional to the radius to thefourth power, a physical principle that becomes sig-nificant with the 20-, 22-, and 24-gauge peripherallines that sometimes are necessary in small childrenpresenting in extremis. Additionally, this assumes thataccess can be obtained readily, which often is not thecase in a small unstable patient. Second, the avail-ability of proper infusion equipment is not wide-spread. The rapid infusers that are used with someregularity in adult medicine are not commonly usedoutside of tertiary-care pediatric trauma bays, oper-ating theaters, and ICUs. Knowledge of the speed offluid delivery of standard intravenous fluid pumpsalso is lacking (eg, most providers would be unawarethat a 20-mL/kg bolus in a child weighing 15 kgwould take 18 minutes to complete for a pumprunning at “maximum”: 999 mL/h). Finally, the needto obtain access and institute fluids rapidly is notuniversally appreciated in pediatric care, an oversightthat global sepsis and shock recognition movementsare now addressing.Clinical examination plays a relatively larger role

in resuscitating children. Assessment of volume andoxygenation debt by thorough examination of thecritically ill child consists of a precise time-stampedinspection of perfusion, capillary refill, skin temper-ature, skin turgor, mucous membranes, lung auscul-tation, cardiac examination, mental statusexamination, and vital signs. Owing in part to theinability to obtain reliable invasive measurements(described in some detail next), pre- and post-examinations of children with fluid resuscitation reston the cornerstones of changes in these physicalexamination findings.Unlike physical signs and symptoms, using surro-

gates of oxygen delivery, including mixed venousoxygen saturation (SvO2), central venous oxygensaturation (ScvO2), and serum lactate concentration,better represents the imbalance between the body’smetabolic demands and the adequate delivery of ox-ygen to body tissues. The SvO2 measurement is ac-quired from the distal port of a pulmonary arterycatheter (PAC). Oxygen consumption exceeding its

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Figure 3. Patient A has a steeper Starling curve than patient B.Although patients A and B have the same initial preload valueand identical changes in preload (ie, fluid bolus), patient A hasa greater increase in stroke volume (SV) than patient B. PatientA is said to be “volume responsive.” Reproduced from Davison &Junker (“Advances in critical care for the nephrologist: hemody-namic monitoring and volume management.” Clin J Am SocNephrol. 2008;3[2]:554-556) with permission of the AmericanSociety of Nephrology.

Figure 4. Patient C is on the steep portion of the curve.Patient D is on a flat portion. Identical changes in preload(ie, fluid bolus) result in different stroke volumes (SVs). Repro-duced from Davison & Junker (“Advances in critical care forthe nephrologist: hemodynamic monitoring and volume manage-ment.” Clin J Am Soc Nephrol. 2008;3[2]:554-556) with permis-sion of the American Society of Nephrology.

Davison et al

supply or oxygen delivery being compromised re-duces subsequent oxygen venous return to the rightside of the heart. An SvO2 , 65% (reference range,65%-75%) reflects an imbalance. An ScvO2 levelobtained from the distal port of a subclavian or in-ternal jugular central catheter can act as a surrogatefor the PAC-derived SvO2. Although the 2 values(SvO2 and ScvO2) are not equivalent, they have beenshown to correlate well. ScvO2 , 70% denotes inad-equate oxygen delivery and should trigger an inter-vention. High serum lactate concentration and theinability to clear this lactate can reflect mitochondrialdysfunction, often as a consequence of inadequateoxygen delivery. As demonstrated by the study byRivers et al, a high lactate level can occur even in thesetting of normal blood pressure and heart rate, andtherefore one should have a very low threshold forobtaining a lactate level in a patient who meets sys-temic inflammatory response syndrome criteria. Iflactate level is high (in general we use a cutoff of2.0 mmol/L), fluid resuscitation followed byrechecking the value 6 hours later to ensure clearanceis a reasonable approach. Studies have shown thatlactate clearance $ 10% is associated with improvedoutcomes and is the basis for this strategy.

Assessment of Fluid Resuscitation Targets

Overview. Given adequate hemoglobin and oxy-gen saturation levels, cardiac output is the maindeterminant of oxygen delivery. Therefore, fluidmanagement should be based on whether giving abolus of fluid infusion augments cardiac output andthus improves perfusion and oxygen delivery (ie,whether cardiac output is fluid responsive). Thisrelationship between preload and cardiac performanceis depicted by the Frank-Starling curve, whereby achange in preload will produce a significant change incardiac output only if both ventricles operate on theascending limb of the Frank-Starling curve (Figs 3and 4). Conversely, if preload value is low, yetoperates on a flat portion of the Frank-Starling curve,volume expansion will not improve cardiac perfor-mance and will only contribute to volume overload. Itis this physiologic concept that governs why a staticvalue of preload does not predict the extent that strokevolume will respond to a volume challenge.In children, the response of the myocardium to

volume resuscitation is different than in adults. Themyocardium in neonates and infants is immaturesecondary to numerous cardinal properties: a lowercontractile to noncontractile ratio, different shape(more circular than elongated/fibrillar), less extracel-lular matrix elements that confer more tensilestrength, decreased myocardial compliance, and lessready regulation of calcium current for depolarization.Though the Starling mechanism is intact, the curve is

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shifted to the left and requires less volume loading toreach higher pressure. In aggregate, volume loadingthe immature myocardium leads to a relativelydecreased effect on augmenting cardiac outputcompared to the mature heart. In addition, the matu-ration process and relative compliance of the ventri-cles, along with intraventricular dependence, changedramatically in the first year of life. Though the right

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Figure 5. Dynamic markers. Pulse pressure (PP) variationrelative to peak airway pressure (Paw) during inspiration andexpiration. Reproduced from Davison & Junker (“Advances incritical care for the nephrologist: hemodynamic monitoring andvolume management.” Clin J Am Soc Nephrol. 2008;3[2]:554-556) with permission of the American Society of Nephrology.

Fluid Management in Adults and Children

ventricle is always more compliant than the leftventricle, the relative abundance of contractile ele-ments in the right ventricle decreases significantlyrelative to the left within the first 3 months of post-natal development. Finally, it is important to recog-nize the inverse relationship of heart rate and strokevolume (or rather, the incomplete inverse relation-ship) in neonates and infants. Because the myocar-dium is limited in tensile strength, neonatal and infanthearts are more dependent on heart rate as a means toaugment cardiac output. Taken together, properties ofthe myocardium are important to recognize because asignificant proportion of mortality from shock andvolume depletion in children occurs in the neonatalperiod.Static measurements. Static markers of preload

include pulmonary artery occlusion pressure (or“wedge”) and central venous pressure. Despite theircommon use in the critical care setting, these pa-rameters are poor surrogates of volume status and failto predict fluid responsiveness, as demonstrated bynumerous studies. In clinical practice, central venouspressure is used as a surrogate for right atrial and rightventricular volumes. Likewise, in theory, pulmonaryartery occlusion pressure represents the volume of theleft side of the heart. Use of these filling pressures as aparameter of volume status assumes a constant rela-tionship between pressure and volume. However,there are several clinical scenarios in which thisrelationship is altered. In the noncompliant “stiff”heart, central venous pressure and pulmonary arteryocclusion pressure may be elevated even if the ven-tricles are underfilled. The high pressure values wouldindicate that the patient is volume replete when inactuality, cardiac performance may still benefit fromvolume. External pressures, including high ventilatorpressures, abdominal compartment pressures, andvascular compliance, can alter the relationship be-tween central venous pressure, pulmonary artery oc-clusion pressure, and ventricular volume, makingthem an inaccurate gauge of volume status. Use ofcentral venous pressure measurement to estimate fluiddynamics in children outside the immediate post-operative congenital cardiac surgery setting has noliterature support. In addition, the relatively higherpressure of the right ventricle in neonates and infants(vs the left as a function of age) affects the reliabilityof the static central venous pressure measurement.We strongly recommend against the use of static

preload markers to define volume status or guideresuscitation.Dynamic measurements. Dynamic markers consist

of variations in stroke volume and arterial pressurethat result from heart-lung interactions during positivepressure ventilation. Many studies have documentedthat these parameters better predict whether volume

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administration will improve cardiac performance.Mechanistically, dynamic measurements are acquiredas follows. With each positive pressure breath, there isa decrease in venous return. If the right ventricle ispreload dependent, there also will be reduced rightventricular outflow. There is a subsequent decrease inleft ventricular outflow (after a few cardiac cycles,given the 2-second transit time for blood to passthrough the lungs). The opposite occurs duringexhalation: venous return is increased and cardiacoutput is amplified. This cyclic variation in strokevolume and blood pressure is most pronounced whenstroke volume is preload dependent. Therefore, highvariations suggest that hemodynamics will benefitfrom volume expansion. Clinically, these markersinclude systolic pressure variation, pulse pressurevariation, and stroke volume variation. An example ofthis physiologic concept is depicted in Fig 5. Thesevalues can be measured on an arterial wave formtracing (systolic pressure variation and pulse pressurevariation) or calculated and displayed continuously byhemodynamic devices (described next). At our insti-tution, we use stroke volume variation as a guide tovolume expansion. Stroke volume variation greaterthan 10%-13% indicates that the patient is fluidresponsive. If a patient has a stroke volume var-iation , 10% and cardiac output unresponsive tovolume, that patient’s hypotension would be managedwith either vasopressors alone or inotropes, depend-ing on cardiac function (Fig 6).The use of dynamic markers to predict fluid

responsiveness has limitations. These markers aremost accurate when used in a mechanically ventilatedpatient with consistent breaths, which usually occurduring deep sedation or paralysis. Few studies havevalidated its use in spontaneously breathing patients.Similarly, in the open-chest patient, ventilator-

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Figure 6. Bedside strategy for fluidmanagement. Abbreviations: CI, cardiacindex; MAP, mean arterial pressure;SIRS, systemic inflammatory responsesyndrome; ScvO2, central venous oxygensaturation; SVV, stroke volume variation.

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induced variation in stroke volume loses its accuracy.Stroke volume variation is not accurate in patientswith arrhythmias.Dynamic markers of fluid responsiveness have not

been assessed adequately in infants, children, andadolescents. Pulse pressure variation and systolicpressure variation analysis in neonates and infants isdiscrepant from children and adolescents secondary tothe differences in chest wall elasticity and lungcompliance as a function of age.Other functional dynamic measurements. Two

other dynamic mechanisms by which fluid respon-siveness can be measured include the passive leg raiseand variation in inferior vena cava (IVC) diameter.During the passive leg raise test, a recumbent patientraises the lower extremities above the heart, whichincreases right and left cardiac preload. If no othermonitoring device is present, the effect of passive legraise on blood pressure and heart rate is used to guidethe decision of whether more fluid is indicated. Thepassive leg raise test reproduces the effects of a vol-ume challenge and therefore also plays a therapeuticrole. The passive leg raise test has proved accurate innonintubated patients, which differentiates it from theother dynamic parameters. The passive leg raise testcannot be performed in immobilized patients (eg,those who have traumatic brain injury or openabdomen). IVC diameter measured by echocardio-gram is another method to measure fluid responsive-ness. Like the other dynamic parameters, variation inIVC diameter depends on the variation in venousreturn as a result of changes in thoracic pressureduring mechanical ventilation. Variation in IVCdiameter is calculated as the change in IVC diameterduring inspiration compared with expiration(approximately .20% variation indicates volume

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responsiveness). Measuring IVC diameter variationrequires echocardiography, which is highly dependenton operator skill. Neither passive leg raise test resultsnor IVC diameter variation can be measured in acontinuous fashion and therefore are not useful forongoing assessment of hemodynamic instability.Tests of reliability for IVC diameter measurement inchildren have not been performed and informal as-sessments of interuser consistency demonstrate a lackof appropriate standards. However, in children, in lieuof a passive leg raise test, direct pressure applied tothe inferior surface of the liver edge often is used as atest of volume responsiveness.

Devices Used for Fluid Management at the Bedside

Pulmonary Artery Catheter

Monitoring devices that display cardiac output andfacilitate the measurement of volume responsivenesscan allow for more precise resuscitation and minimizeunwanted side effects. The gold standard formeasuring bedside cardiac output is the PAC. ThePAC uses the thermodilution technique to calculatecardiac output, and it is the mechanism against whichall other devices are measured. Central venous pres-sure, right atrial pressure, pulmonary artery pressures,pulmonary artery occlusion pressure, and ScvO2 alsocan be obtained from the PAC. Newer fiberopticPACs allow for continuous cardiac output moni-toring, which adds significant clinical value whenmonitoring trends and changes in intervention. Use ofPACs has declined in the past 20 years for 2 majorreasons. First, despite a large body of research, thePAC has never been shown to improve outcomes.Second, the advent of newer devices that are lessinvasive and provide dynamic parameters to assess

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volume responsiveness are making the PAC increas-ingly obsolete. Though no evidence demonstratesproven efficacy of the PAC at reducing mortalityacross the wide range of critically ill children, therealso is no solid evidence indicating an increase inmortality or complications. The available data supportusing PACs in select children (those with pulmonaryhypertension and refractory shock). Pediatric criticalcare practitioners continue to use PACs, though atlower numbers, driven by clinical context.

Less Invasive Hemodynamic Devices

Echocardiography. Echocardiography is a nonin-vasive technique that uses ultrasound waves togenerate real-time images of the heart. It is usedincreasingly by intensivists to gain a snapshot ofventricular function and volume status. It rarely isused in a continuous fashion outside the operatingroom and therefore has its limitations for ongoingmanagement of critically ill patients.Esophageal Doppler. This technique estimates

aortic blood flow through a Doppler ultrasoundinserted into the esophagus. It is based on the physi-ologic concept that the velocity of blood flow throughthe aorta is inversely proportional to aortic diameterand directly related to flow. This technique requiresthat the patient be intubated on insertion and that flowis laminar throughout the aorta. Turbulent flow sec-ondary to atherosclerosis or an aneurysm will distortthe calculations of cardiac output. This technique alsorelies heavily on operator skill for proper placementof the device in the esophagus. Despite these draw-backs, data suggest that esophageal Doppler is areliable measure of continuous cardiac output.Thoracic electrical bioimpedance. Bioimpedance

is the electrical resistance of the thorax to an alter-nating electrical current transmitted through the chest.This is accomplished by 8 electrodes placed on thepatient’s thorax and connected to the thoracic elec-trical bioimpedance device. The patient’s cardiacoutput is calculated using the impedance of thethoracic aorta, which varies with blood flow. Thoracicelectrical bioimpedance is noninvasive; however, itloses accuracy in the settings of pulmonary edema,pleural effusions, and chest wall edema due to thefluid interference. Studies have not demonstrated thatthoracic electrical bioimpedance is an accurate mea-sure of cardiac output; it should be used in only aselect set of patients.Transpulmonary thermodilution. The trans-

pulmonary thermodilution technique uses thermodi-lution similar to that of the PAC. However, it requiresuse of a standard central venous catheter in the in-ternal jugular or subclavian vein, as well as a distalthermistor tip in the femoral artery. Cold injectate isinfused into the central line and the temperature

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change as measured in the downstream femoral arterythermistor is used to calculate cardiac output.Assuming minimal loss of injectate and only one passfrom the proximal to distal thermistor, this is an ac-curate measure of cardiac output. A unique feature ofthe transpulmonary thermodilution technique is that italso allows for calculation of global end-diastolicvolume and extravascular lung water, which reflectcardiac filling and pulmonary edema, respectively.Studies have shown this technique to be a reliablemeasure of cardiac output in the critically ill patientpopulation.Lithium dilution. In this technique, a bolus of

lithium is injected into a venous catheter. Blood thenis drawn from a distal arterial catheter that contains alithium sensor. The dilutional curve over time is usedto estimate cardiac output. Unlike the transpulmonarythermodilution technique, lithium dilution does notrequire a central venous catheter, but it requiresarterial access and is dependent on accurate sodiumand hemoglobin concentrations. Lithium dilution iscontraindicated in patients receiving lithium therapy,those who weigh ,40 kg, and those who are preg-nant. Lithium dilution also can calculate extravascularlung water and compares well when measured againstother thermodilution techniques.Pulse contour analysis. Pulse contour analysis is a

unique monitoring system that displays cardiac outputand cardiac index, stroke volume and stroke volumeindex, and the dynamic marker stroke volume varia-tion, all in a continuous fashion. Pulse contour anal-ysis is based on the notion that the pulse pressurearterial waveform is proportional to stroke volumeand inversely related to compliance of the vessel.Cardiac output is calculated from the analysis of thepulse contour. PICCO (Pulsion Medical Systems),PulsCO (LidCO Ltd), and FloTrac (Edwards Life-science LLC) are the 3 pulse contour analysis devicesavailable on the market. We use the FloTrac at ourinstitution, which is the only device that does notdepend on recalibration and requires only an arterialline. PICCO must be recalibrated using the trans-pulmonary thermodilution technique and thereforerequires both central venous access and a femoralarterial catheter. PulsCO must be recalibrated every8 hours and uses the lithium dilution technique to doso. Although most studies have demonstrated that thepulse contour analysis technique is accurate andreliable, there are some limitations. Because it relieson the shape of the arterial waveform, a dampenedarterial line tracing, the presence of atherosclerosis, orany arrhythmias, including frequent premature ven-tricular contractions, can generate inaccurate data.Alterations in chest wall compliance or certainventilator settings (eg, elevated positive end-expiratory pressure) can affect the accuracy of pulse

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contour analysis. This monitoring system has not beenvalidated in spontaneously breathing patients. Last,these devices can be costly and therefore might notavailable in settings in which resources are limited.Optical-based assessment of tissue perfusion.

Near-infrared spectroscopy is a transcutaneous moni-toring system that acts as a surrogate for tissue meta-bolism. Displaying results as regional oxygensaturation, near-infrared spectroscopy technology re-lies on the emission of infrared light to millimetersdeeper than the traditional pulse oximeter. This tech-nique differentiates between oxygenated and deoxy-genated moieties (not simply red blood cells). Thealgorithm within the individual near-infrared spec-troscopy devices is able to detect changes in deoxy/oxycomponents of the subdermal microcirculation andacts as a real-time sensor of oxygen delivery andconsumption. Though rigorous study and evaluation ofnear-infrared spectroscopy currently is unavailable,there are numerous reports of near-infrared spectros-copy monitoring systems foretelling acute decom-pensation events, near-infrared spectroscopy valuesresponding to vigorous resuscitations (ie, code events)and fluid resuscitations, and cerebral near-infraredspectroscopy being a sensitive indicator of acutebrain attacks (strokes). However, this technology re-mains unproved versus gold-standard measurements.

Additional Readings

» Busse L, Davison D, Junker C, Chawla LS. Hemodynamicmonitoring in the critical care environment. Adv ChronicKidney Dis. 2013;20(1):21-29.

» Carcillo J, Davis A, Zaritsky A. Role of early fluid resusci-tation in pediatric septic shock. JAMA. 1991;266(9):1242-1245.

» Davison D, Junker C. Advances in critical care for thenephrologist: hemodynamic monitoring and volume man-agement. Clin J Am Soc Nephrol. 2008;3(2):554-561.

» Harvey G, Parker M. Fluid resuscitation targets, how do weget there? McMaster University Med J. 2009;2(9):39-41.

» Jones AE, Shapiro NI, Trzeciak S, Arnold RC, ClaremontHA, Kline JA. Lactate clearance vs. central venous oxygensaturation as goals of early sepsis therapy. JAMA.2010;303(8):739-746.

» Lin SM, Huang CD, Lin HC, Liu CY, Wang CH, Kuo HP. Amodified goal-directed protocol improves clinical outcomesin intensive care unit patients with septic shock: a randomizedcontrolled trial. Shock. 2006;26(6):551-557.

» Marik PE, Baram M. Noninvasive hemodynamic monitoringin the intensive care units.Crit Care Clin. 2007;23(3):383-400.

» McGee WT. A simple physiologic algorithm for managinghemodynamics using stroke volume and stroke volumevariation: physiologic optimization program. J Intensive CareMed. 2009;24(6):352-360.

» Perkin R, Anas N. Pulmonary artery catheters. Pediatr CritCare Med. 2011;12(4 suppl):S12-S20.

» Pinsky MR. Hemodynamic evaluation and monitoring in theICU. Chest. 2007;132(6):2020-2029.

» Price JF. Unique aspects of heart failure in the neonate. In:Shaddy R, ed. Heart Failure in Congenital Heart Disease.2nd ed. Philadelphia, PA: Springer Publishing; 2011.

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» Rivers E, Nguyen B, Havstad S, et al. Early goal-directedtherapy in the treatment of sepsis and septic shock. N EnglJ Med. 2001;345(19):1368-1377.

» Scheeren TW, Schober P, Schwarte LA. Monitoring tissueoxygenation by near infrared spectroscopy (NIRS): back-ground and current applications. J Clin Monit Comput.2012;26(4):279-287.

Dangers of Fluid Resuscitation

As emphasized, early targeted fluid resuscitationto optimize tissue perfusion is the key to managingpatients who are hemodynamically unstable. However,continued volume resuscitation beyond what willimprove hemodynamics has detrimental effects.Increasing evidence is demonstrating that a positivefluid balance is associatedwithworse outcomes. Single-center data initially suggested that increased fluidoverload percentage at the time of RRT initiation wasassociated with higher mortality in 2001. Since thattime, data from more than 13 separate centers in theProspective Pediatric Continuous Renal ReplacementTherapy (ppCRRT) Registry comprising 300 patientscontinues to indicate that a high fluid overload per-centage is associated with worsened outcomes (highermortality and longer duration of mechanical ventila-tion). Note that the calculation for fluid overloadpercentage (FO%) is: FO%5 (cumulative fluid in2cumulative fluid out)/weight (kg). Data from adultshave paralleled this finding. A summary of the organ-specific consequences of overzealous fluid therapyis next.

Vasculature

Mediated by atrial natriuretic peptide release,excess fluid can lead to degradation of the glycocalyxbarrier, ultimately increasing vascular permeabilityand promoting tissue edema. A viscious cycle ofrepeated boluses to maintain intravascular volumemay ensue, which further contributes to the underly-ing pathophysiology.

Cardiac

Increased ventricular wall stretch, functional mitraland tricuspid insufficiency, resultant pulmonary hy-pertension, and exacerbation of diastolic dysfunctionare all consequences of fluid accumulation.

Lungs

The consequence of fluid overload is most apparentin the lungs, in which pulmonary congestion causesincreased workload and reduced compliance. TheFACTT (Fluids and Catheters Treatment Trial)demonstrated that patients who received a restrictedfluid regimen compared to a liberal regimen spent lesstime on the ventilator and less time in the ICU.Similar findings were seen in an observational studyof brain-dead organ donors in which a restricted fluidstrategy resulted in an increase in number of lung

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procurements. The fluid restriction did not negativelyaffect kidney transplant function. In a single-centerstudy of 80 mechanically ventilated children, fluidoverload began to be correlated positively and inde-pendent with worsening oxygenation index at 15%relative volume accumulation.

Kidneys

As an encapsulated organ, the kidney has limitsof expansion when edematous. On a mechanisticlevel, an increase in kidney venous pressure due tofluid overload decreases kidney arterial perfusion,increases interstitial pressure, and stimulates therenin-angiotensin system, which worsens fluid accu-mulation. There are convincing data to show thatvolume overload at the time of dialysis initiation isassociated with heightened mortality and decreasesthe likelihood of recovering kidney function. More-over, no randomized controlled trials have demon-strated that a positive fluid balance prevents kidneyinjury during acute illness, whereas a 5%-10% in-crease in water weight is associated with worseningorgan function in patients with AKI.

Gastrointestinal/Abdominal Compartment

Postoperative ileus and malabsorption are pro-longed as a consequence of fluid overload. Arestricted fluid strategy has been shown to be asso-ciated with decreased incidences of complicationsafter colorectal surgery, including anastomotic leaks,pulmonary edema, wound infection, and AKI. Intra-abdominal hypertension and abdominal compart-ment syndrome are major consequences of imprudentresuscitation. Intra-abdominal hypertension causesdecreased venous return, decreased ventilatorcompliance, reduced renal blood flow, and subsequentdevelopment of shock and AKI.

Tissue Edema

Once thought of as simply a cosmetic concern,tissue edema now is linked to impaired oxygendiffusion, obstruction of capillary blood flow andlymphatic drainage, poor wound healing, and thedevelopment of pressure ulcers.

Immune System

The innate immune response, particularly to sepsis,may be aberrant in fluid overload states. Responses ofhumoral cytokines such as TNF-a, IL-4, IL-6, IL-10,and monocyte chemotactic protein 1 reportedly havebeen altered in animal models of sepsis with fluidoverload. Additionally, response of the Toll-like re-ceptor family to pathogen-associated molecular pat-terns may be hampered in fluid overload states.Fluid is a drug and should be treated as one. Given

the body of evidence reviewed, we propose thatintravenous fluid be viewed as a prescribed medication

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with indications, contraindications, and side effects.The correct “dose” is specific to each individualbased on his or her physiologic needs and canchange dramatically within hours of illness presen-tation. Recognizing and maintaining adequate oxy-gen delivery with fluid administration early in thecourse of illness will improve outcomes. However,when a patient is volume replete, we advise a strat-egy of fluid restriction and diuresis to prevent ormanage volume overload. Too often, fluid manage-ment is left to the discretion of an inexperiencedphysician who indiscriminately gives a fluid bolus tothe hypotensive or oliguric patient. Based on dy-namic parameters and hemodynamic monitoring,this patient may benefit from other interventions,such as pressors, inotropes, or diuresis. Figure 6provides a schematic algorithm that can help thebedside clinician in ensuring organ perfusion whileavoiding volume overload.

Additional Readings

» Arikan AA, Zappitelli M, Goldstein SL, Naipaul A, JeffersonLS, Loftis LL. Fluid overload is associated with impairedoxygenation and morbidity in critically ill children*. PediatrCrit Care Med. 2012;13(3):253-258.

» Bouchard J, Soroko SB, Chertow GM, et al. Fluid accumu-lation, survival and recovery of kidney function in criticallyill patients with acute kidney injury. Kidney Int.2009;76(4):422-427.

» Boyd JH, Forbes J, Nakada T, Walley KR, Russell JA. Fluidresuscitation in septic shock: a positive fluid balance andelevated central venous pressure are associated with increasedmortality. Crit Care Med. 2011;39(2):259-265.

» Goldstein SL. Advances in renal replacement therapy inchildren. Semin Nephrol. 2011;24(2):187-191.

» Miñambres E, Rodrigo E, Ballesteros MA, Llorca J, Ruiz JC,Fernandez-Fresnedo G. Impact of restrictive fluid balancefocused to increase lung procurement on renal function afterkidney transplantation. Nephrol Dial Transplant.2010;25(7):2352-2356.

» Payen D, de Pont AC, Sakr Y, et al. A positive fluid balanceis associated with a worse outcome in patients with acuterenal failure. Crit Care. 2008;12(3):R74.

» Sutherland SM, Zappitelli M, Alexander SR, et al. Fluidoverload and mortality in children receiving continuous renalreplacement therapy: the Prospective Pediatric ContinuousRenal Replacement Therapy Registry. Am J Kidney Dis.2010;55(2):316-325.

» Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in Europeanintensive care units: results of the SOAP Study. Crit CareMed. 2006;34(2):344-353.

» Weidemann HP, Wheeler AP, Bernard GR, et al. Comparisonof two fluid-management strategies in acute lung injury. NEngl J Med. 2006;354(24):2564-2575.

TAKE HOME POINTS

Without evidenced-based guidelines to direct vol-ume management, it is essential to understand theunderlying physiology, including vascular integrityand fluid shifts, in order to make a rational choice

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of the type, amount, and mechanism by which tomonitor fluid therapy.In today’s health care environment, in which cost

savings and patient safety are paramount, focusing onthe overall cost and side effects of each individualfluid should be the main determinant of which fluid tochoose. We recommend using balanced crystalloidsolutions for resuscitative purposes, with the additionof albumin in select patients.Securing adequate intravascular volume to opti-

mize the delivery of oxygen to tissues is the primarygoal of resuscitation. Using surrogates of delivery andextraction, including SvO2, ScvO2, and lactate levels,can help identify patients with global oxygen debt.The main determinant of oxygen delivery to organs

is cardiac output. Static measurements, includingcentral venous pressure and pulmonary artery occlu-sion pressure, are not valid markers of intravascularvolume status. Dynamic monitors better assesswhether volume will improve cardiac output and thedelivery of oxygen to tissues.

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Monitoring devices that display dynamic variablesand cardiac output in a continuous fashion can beinstrumental to ensuring that bolus administration isboth timely and appropriate.Continued volume resuscitation beyond what will

improve hemodynamics has detrimental effects. Fluidis a drug and is prescribed, dosed, and delivered likeall other medications. Overdose is a possibility andtoo often is a reality. When hemodynamic goals havebeen met, one should consider a strategy of fluid re-striction or diuresis.Resuscitation of children must take into consider-

ation the unique features of children’s physiology,particularly in neonatal and infant patients who haveless myocardial and pulmonary reserve in addition toimmature capabilities of handling salt and water.

ACKNOWLEDGEMENTSSupport: None.Financial Disclosure: The authors declare that they have no

relevant financial interests.

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