IIn a healthy adult, nearly all fluid is contained inthe intracellular, intravascular, or interstitialspaces, with the intracellular space holding abouttwo-thirds of total body water. Normally, fluidmoves freely between these three spaces to main-tain fluid balance (see Water, water everywhere).

Third-spacing occurs when too much fluid movesfrom the intravascular space (blood vessels) intothe interstitial or “third” space—the nonfunctionalarea between cells. This can cause potentially seri-ous problems such as edema, reduced cardiacoutput, and hypotension.

In this article, I’ll describe why third-spacingoccurs and how to intervene to restore balance.Let’s start with a brief physiology review.

What’s behind third-spacing?Fluid volume, pressure, and levels of sodiumand albumin are the keys to maintaining fluidbalance between the intracellular and extracellu-lar (intravascular and interstitial) spaces. Capillarypermeability and the lymphatic system also playa role. A problem with any of these componentscan cause fluid to shift from the intravascular spaceto the interstitial space. Let’s look more closely ateach component.• Increased fluid volume can be caused by overzealousfluid replacement or renal dysfunction. Volumeoverload can lead to peripheral edema, pulmonaryedema, hepatic dysfunction, cerebral edema andmental changes, and decreased cardiac output. Othersigns of fluid overload include jugular vein distension,hypertension, and a pathologic S3.• Increased capillary hydrostatic pressure oftenaccompanies heart failure. Right-sided heartfailure is characterized by an increase in venouspressure that causes edema in the liver and theperiphery. Left-sided heart failure causes pul-monary edema.• Decreased sodium level, or hyponatremia, may resultfrom sodium loss; for example, gastrointestinal

losses during diarrhea or fluid losses caused bymedications such as diuretics. Hyponatremia canalso arise from volume overload. Also called dilu-tional or hypervolemic hyponatremia, this canoccur with overzealous fluid replacement, heartfailure, hepatic cirrhosis, renal disease, hypothy-roidism, or administration of vasopressin. • Albumin losses disrupt colloidal osmotic pressure.Plasma proteins are crucial to maintaining colloidalosmotic pressure. Albumin, the major protein con-stituent of the intravascular space, accounts for upto 60% of total protein. Any condition that destroystissue or reduces protein intake can lead to proteinlosses and third-spacing. Some examples arehypocalcemia, decreased iron intake, severe liverdiseases, alcoholism, hypothyroidism, malabsorption,malnutrition, renal disease, diarrhea, immobility,burns, and cancer.

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T o p i c s i nP r o g r e s s i v e C a r e

Third-spacing: When body fluid shiftsBy Susan Simmons Holcomb, ARNP-BC, PhD

Water, water everywhere

Body fluids are distributed between the intracellularand extracellular fluid compartments. The intracellularcompartment consists of fluid contained within all thebody cells. The extracellular compartment contains allthe fluids outside the cells, including fluid in the inter-stitial (tissue) spaces, and that in the intravascularspace (blood vessels).

Intracellular fluid

Intravascular fluid

Interstitial fluid

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T o p i c s i nP r o g r e s s i v e C a r e

• Increased capillary permeability resultsfrom burns and other forms of tissuetrauma. Edema due to an increase incapillary permeability can be local, aswith a localized trauma, or systemic aswith anaphylaxis or disseminatedintravascular coagulation.• Lymphatic system obstruction is com-monly caused by lymph noderemoval to treat cancer. An obstruc-tion typically leads to localizededema; fluid and plasma proteinsaccumulate and can’t be drained intothe general circulation because of thelymphatic obstruction (see The role ofthe lymph system). Postmastectomylymphedema is an example of thistype of third-spacing.

Phases of third-spacingThird-spacing has two distinct phases—loss andreabsorption.

In the loss phase, increased capillary permeabilityleads to a loss of proteins and fluids from theintravascular space to the interstitial space. Thisphase lasts 24 to 72 hours after the initial insultthat led to the increased capillary permeability(for example, surgery, trauma, burns, or sepsis).Fluid loss from diarrhea, vomiting, or bleeding canbe measured, but fluid loss from third-spacing isn’t soeasy to quantify. Signs and symptoms include weightgain, decreased urinary output, and signs of hypo-volemia, such as tachycardia and hypotension.

During the reabsorption phase, tissues begin to healand fluid is transported back into the intravascularspace. Signs of hypovolemia resolve, urine outputincreases, the patient’s weight stabilizes, and signsof shock (if any) begin to reverse. If the patientwas given fluid resuscitation during the loss phase,monitor for fluid overload as interstitial fluid shiftsback to the intravascular space.

Determining the causeIn some cases, the cause of third-spacing may besubtle and require a diagnostic workup, including acomplete blood cell count (CBC), complete metabol-ic profile, and serum osmolality. The CBC may giveclues to volume status and factors contributing tothird-spacing, such as infection or necrosis. Elevatedhemoglobin and hematocrit values may indicate

hypovolemia; decreased values may indicate hyper-volemia. The metabolic panel will give clues to renaland hepatic function as well as electrolyte balance(especially sodium), and levels of protein, includingalbumin.

The albumin-to-globulin ratio (normally slightlygreater than 1:1) will elicit more information aboutcolloidal osmotic pressure than total protein andalbumin levels alone. Albumin molecules are largeand don’t diffuse freely through the vascularendothelium, making this protein a major sourceof plasma colloid osmotic pressures.

Noninvasive assessment tools include an echocar-diogram, which may yield information on cardiacfunction and volume status, and weighing thepatient daily. Invasive hemodynamic monitoring ofcentral venous pressure, right atrial pressure, andpulmonary artery occlusive pressure also help trackvolume status and the patient’s response to treat-ment for hypervolemia or hypovolemia. However,some patients aren’t candidates for hemodynamicmonitoring, and some facilities aren’t equipped forthis type of monitoring.

Treatment of third-spacing depends on the cause,the phase, and the factors involved. Stabilizing yourpatient’s hemodynamic status is the first priority.During the loss phase, your focus is on preventinghypovolemia and hypotension, which can lead toshock and renal failure. During the reabsorptionphase, focus on preventing circulatory overload andhypertension, which can lead to pulmonary edema.

The role of the lymph systemNormally the forces moving fluid out of the capillaries into the interstitialspace are greater than those returning fluid to the capillaries. The lym-phatic system usually returns excess fluids and osmotically active plas-ma proteins to the circulation. But if the lymphatic system is obstructed,fluid and plasma proteins accumulate in the interstitial space.

Arterial endVenous end

Capillary

Excess fluid and proteins accumulate in interstitial space

Obstructed lymphatic vessel

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Which fluid is best? To stabilize the patient’s volume status, you’lladminister crystalloids, colloids, or a combinationof these. Crystalloids replace electrolytes andrestore normal serum osmolality; colloids replacethe proteins responsible for maintaining plasmacolloid osmotic pressure. Crystalloids are mostcommonly used, and can also treat hyponatremia.Remember, you’re trying to replenish intravascu-lar volume, not deplete the third space.

Crystalloid fluids can be hypotonic, isotonic,or hypertonic. Hypotonic solutions, such as 0.45%sodium chloride solution, aren’t appropriate forvolume resuscitation because very little of thefluid would remain in the intravascular space.

Isotonic solutions such as lactated Ringer’s solu-tion and 0.9% sodium chloride solution, which aresimilar to plasma in tonicity and osmolality, are usedfor resuscitation, with 0.9% sodium chloride solutionpreferred if the patient is hyponatremic.

Hypertonic solutions, such as 3% sodium chloridesolution, contain large amounts of sodium and havebeen rarely used for resuscitation because of theirpotential for cellular dehydration and overexpansionof the intravascular space. However, a recent studyfound that hypertonic crystalloids were better thanisotonic crystalloids for reducing abdominal third-spacing and abdominal compartment syndrome thatoften occur with massive fluid resuscitation inpatients with extensive burns.1 Another study ofcritically ill patients found that even though smallervolumes of hypertonic solutions are needed for fluidresuscitation, there wasn’t enough evidence to deter-mine whether hypertonic solutions were safer ormore effective than isotonic solutions.2

In 2004, the SAFE (saline versus albumin fluidevaluation) study evaluated fluid resuscitation withalbumin, a colloid, compared with crystalloid.3 Thestudy found that albumin wasn’t associated withhigher morbidity and mortality in critically illpatients. In young adult trauma patients withoutpreexisting cardiovascular or pulmonary disease,resuscitation with albumin or 0.9% sodium chloridesolution may not make a difference except in cost:Albumin is considerably more expensive. However,with older adults, patients with associated traumaticbrain injury, and patients with cardiovascular orpulmonary disease, colloid use was found to beassociated with increased morbidity and mortalitycompared with crystalloid use.4 At present, due to

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the cost of colloids and the potential for adverse reac-tions, especially if human albumin is used, researchdoesn’t support using colloids instead of crystalloids.4

No matter which type of fluid he receives, monitoryour patient’s response to treatment to determine ifthe goals of intravascular resuscitation have been met.

What the future holdsAlthough they’re valuable indicators of a patient’scondition, vital signs, weight, and urine output don’ttell us what’s going on at the capillary level. Futuregoals for treating third-spacing may focus less on thetype of fluid given than the patient’s capillary healthas defined by capillary permeability and perfusion.

Someday soon, we may be able to not only moni-tor capillary health at the bedside, but also to deter-mine which factor or combination of factors led tothird-spacing so that interventions can be tailoredmore precisely to the patient’s condition. ❖

REFERENCES1. Oda J, Ueyama M, Yamashita K, et al. Hypertonic lactated salineresuscitation reduces the risk of abdominal compartment syndrome

in severely burned patients. J Trauma. 2006;60(1):64-71.2. Bunn F, Roberts I, Tasker R, Akpa E. Hypertonic versus near iso-tonic crystalloid for fluid resuscitation in critically ill patients.Cochrane Database Syst Rev. 2004(3):CD002045.3. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R.The SAFE Study Investigators. A comparison of albumin and salinefor fluid resuscitation in the intensive care unit. New Engl J Med.2004;350(22):2247-2256.4. Roberts I, et al. Colloids versus crystalloids for fluid resuscita-tion in critically ill patients. Cochrane Database Syst Rev.2004;18(4):CD000567.

RESOURCESRedden M, Wotton K. Clinical decision making by nurses when facedwith third-space fluid shift: How well do they fare? GastroenterologyNurs. 2001;24(4):182-191.Rizoli S. Crystalloids and colloids in trauma resuscitation: A briefoverview of the current debate. J Trauma. 2003;54(5 suppl.):S82-S88.van Wissen K, Breton C. Perioperative influences on fluid distribu-tion. Medsurg Nurs. 2004;13(5):304-311.Verdant C, DeBacker D. How monitoring of the microcirculationmay help us at the bedside. Cur Opin Crit Care. 2005;11(3):240-244.Vincent JL, Gerlach H. Fluid resuscitation in severe sepsis and septic shock: An evidence based review. Crit Care Med. 2004;32(11 suppl.):S451-S454.

Susan Simmons Holcomb is a nurse practitioner at Olathe (Kan.) MedicalServices, Inc., and a consultant in continuing nursing education at KansasCity (Kan.) Community College.

Adapted from: Holcomb SS. Third spacing: when body fluid shifts. Nursing.2008;38(7):50-53.

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