Fluid Resuscitationof theThermallyInjured Patient

Robert Cartotto, MD, FRCS(C)a,b,*

KEYWORDS� Burns � Fluid resuscitation � Fluid creep� Burn shock � Parkland formula

Acute fluid resuscitation is fundamental to modern IMPORTANT HISTORICAL DEVELOPMENTS

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burn care. Plastic surgeons in many parts of theworld are involved in the acute care of thermallyinjured patients and as such should have an up-to-date understanding of the current approachesto acute fluid resuscitation. For decades, fluidresuscitation has been progressively streamlinedinto a relatively ‘‘routine’’ process of usinga formula to derive a weight and burn size adjustedvolume of fluid, which is then infused into theacutely burned patient, aiming to optimize a varietyof somewhat loosely defined end points led chieflyby urinary output (UO). In recent years, however,there has been an important shift in the under-standing of and approach to fluid resuscitation, fu-eled largely by increasing recognition that moderncrystalloid resuscitation frequently providessubstantial volumes of fluid, often in excess ofthat predicted by current formulas, resulting innumerous edema-related complications (Fig. 1).This phenomenon, coined ‘‘fluid creep’’ by Pruitt,1

is now a topic that dominates most current discus-sion of fluid resuscitation. It is increasingly recog-nized that fluid resuscitation is anything buta rote, standardized process, and that there is anurgent need for re-evaluation of existing resuscita-tion approaches to avoid fluid creep. This articlefamiliarizes plastic surgeons with current conceptsin burn shock and edema formation physiologyand current resuscitation strategies. An importanttheme throughout this article is the understandingof why fluid creep is so prevalent, and what strat-egies can be used to minimize it.

a Department of Surgery, University of Toronto, Torontob Ross Tilley Burn Centre, Sunnybrook Health Sciences CCanada M4N 3M5* Ross Tilley Burn Centre, Sunnybrook Health Sciences CCanada M4N 3M5.E-mail address: robert.cartotto@sunnybrook.ca

Clin Plastic Surg 36 (2009) 569–581doi:10.1016/j.cps.2009.05.0020094-1298/09/$ – see front matter ª 2009 Elsevier Inc. All

Before the 1940s patients with moderate and largeburns commonly developed hypovolemic shock,which resulted in acute renal failure and eventuallydeath in many cases. Two mass casualty fires inNorth America, the Rialto Theater fire in 1921and the Cocoanut Grove Nightclub fire in 1942,led to important advances in the understandingof the burn shock process, and the need to treatthis with early provision of intravenous fluid basedon burn size and weight of the patient.2,3 A host offormulas, which varied in the type of crystalloid,the proportion of colloid administered, and thetiming of administration of these fluids, subse-quently followed4–6 and culminated in the Parklandformula proposed by Baxter and Shires in 1967.7

The Parkland formula, which is the dominantburn resuscitation strategy in North Americatoday, was derived from empiric experiments onburned dogs, and subsequent testing amongseveral hundred human burn patients.7–9

Baxter explicitly stated that most burn patientscould be successfully resuscitated by providingfluid within the relatively narrow range of 3.7 to4.3 mL/kg/% total body surface area (TBSA).10

After more than four decades of acceptance ofthe Parkland formula as a cornerstone of burncare, and despite the fact that this approach hasprovided effective resuscitation that has markedlyreduced the incidence of burn shock-inducedacute renal failure,11,12 several reports haverecently surfaced that show that modern burn

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Fig. 1. An elderly patient recently treated demon-strating ‘‘fluid creep.’’ The patient had a 25% TBSAfull-thickness burn but no smoke inhalation 16 hourspreviously. The patient had been managed withoutendotracheal intubation initially. At 15 hours post-burn he had received 7901 mL of cumulative fluid,which was 62% greater than what the Parklandformula would have predicted to this time point,despite UO averaging only 48 mL/h (0.7 mL/kg/h)over this time period. He began to develop early signsof edema-related upper airway obstruction andrequired prophylactic intubation.

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clinicians are providing volumes that are substan-tially in excess of Baxter’s original recommenda-tions.13–18 Not surprisingly, as a consequence ofthese large resuscitation volumes, complicationsrelated to edema formation led chiefly bysecondary abdominal compartment syndrome(ACS), have also appeared. Current research in fluidresuscitation now concentrates on approaches tominimize fluid creep, including tighter control of fluidinfusion rates, earlier and more liberal use ofcolloids, and the use of hypertonic saline (HTS).

PATHOPHYSIOLOGYOF BURN SHOCKAND EDEMA FORMATION

Familiarity with the pathophysiology of burn shockand edema formation is necessary to understandcurrent fluid resuscitation guidelines and thepossible causes and correction of fluid creep.This section reviews the normal forces that controlmovement of fluid across the capillary membrane,and how these are altered following thermal injury.An excellent review of this topic has recently beenpublished by Demling.19

Burn shock is a form of hypovolemic shock thatarises as a result of the translocation of isotonicprotein-containing fluid from the vascular spaceinto the interstitial space, resulting in edema.19

The contraction of the intravascular space goes

hand-in-hand with development of edema of thesoft tissues. Significant edema is the hallmark ofmoderate to large burn injuries, and is worsenedby fluid resuscitation itself. Fluid resuscitationmay produce acute weight gains of as much as20%, purely on the basis of retained resuscitationfluid.20,21 Most of the edema fluid is found in andsurrounding the burn wound within the interstitialspace of the skin and subcutaneous soft tissueplanes, and to a lesser extent within the cells ofthese tissues. Intracellular edema is seen incombination with accumulation of sodium withincells and a drop in the transmembrane electricalpotential of these cells.22 Although incompletelyunderstood, a circulating shock factor may bepartly responsible for the intracellular accu-mulation of water and sodium and reduction oftransmembrane potential.23 When burn sizeapproaches 25% TBSA or greater, edema alsoforms in the nonburned soft tissues distant fromthe burn wound, including the lung, muscles, andintestines. The amount of edema in the nonburntissues is directly proportional to the burn size.24,25

Direct thermal damage is partly responsible forthe alterations in the burn wound that aredescribed next. Locally released inflammatorymediators, however, play an even more significantrole. Discussion of the complex interactions of theinflammatory mediators is beyond the scope ofthis article but suffice it to say that neutrophils,oxygen-free radicals, prostaglandins and leukotri-enes, kinins, serotonin, and histamine are all impli-cated in the pathogenesis of edema formationpostburn injury.19

Normal Starling Forces

The normal forces that control the movement offluid across the capillary membrane were originallyelucidated by the physiologist Starling in 1896.26

Subsequent refinements of his observationsresulted in the well-known Starling equation:

Q 5 Kf

�Pcap � Pi

�1s�pp � pi

�

At the outset this formula usually seems daunt-ing to most readers, but it can easily be under-stood by breaking it down into its five maincomponents (Fig. 2).

Q is the fluid filtration rate and is simply the rateat which fluid moves (or ‘‘fluxes’’) from the vascularspace, across the capillary membrane, into theinterstitial space. Under normal circumstancesany fluid entering the interstitium is equallyremoved by the lymphatics, so that edema doesnot form.

Kf is the fluid filtration coefficient, which isa measure of how easily fluid is able to move

Fig. 2. Diagram summarizing forces acting across the capillary membrane. Pcap-Pi is the capillary hydrostatic pres-sure gradient; pcap-pi is the colloid osmotic pressure gradient; Kf is the fluid filtration coefficient; s is the reflec-tion coefficient.

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across the capillary membrane and into the inter-stitial space. This depends on the properties ofthe capillary membrane itself, especially thesurface area of the capillary membrane surface inquestion (ie, larger areas facilitate movement),and the actual compliance of the interstitium.19 Inthe case of the skin and surrounding soft tissueplanes the compliance depends on the structuralintegrity of the collagen fibers and the hyaluronicacid linkages between them and the density andhydration of the ground substance in which thesemolecules are embedded. If the collagen frame-work is destroyed and the ground substancebecomes more hydrated (eg, by burn injury fol-lowed by early edema formation), complianceincreases and the ease of fluid movement intothe interstitium increases.27,28

Pcap – Pi is the gradient in hydrostatic pressurebetween the capillary pressure (Pcap) and the inter-stitial hydrostatic pressure (Pi). The gradient isnormally 10 to 12 mm Hg in dermis19 and is ina direction favoring fluid movement out of thecapillary into the interstitium. A higher gradient(eg, caused by an elevation of Pcap or a reductionin Pi) pushes more fluid out and increases Q. Wereit not for an opposing force (the colloid osmoticpressure gradient, described next), fluid wouldcontinually seep out of the capillary into theinterstitium.

pp – pi is the colloid osmotic pressure gradientrepresenting the difference between the plasmacolloid osmotic pressure (pp) and the interstitialcolloid osmotic pressure (pi). This gradient is alsonormally 10 to 12 mm Hg in the dermis but is inthe direction favoring fluid retention within thecapillary because of the higher concentration of

protein within the plasma relative to that in theinterstitial space. The pp – pi counterbalancesthe opposing hydrostatic gradient (Pcap – Pi), sothat edema does not normally develop. If pp

were to decrease significantly (eg, as in hypopro-teinemic states) then pp – pi decreases leavingthe hydrostatic gradient (Pcap – Pi) unopposed,which allows increased fluid flux (Q) into the inter-stitial space.19

s is the reflection coefficient and represents thedegree of capillary membrane permeability. Animpermeable membrane has a s of 1, whereasa freely permeable membrane has a s of 0. Normaldermal capillaries have a s of 0.9.19

Altered Starling Forces in the Burn Wound

Q is dramatically increased immediately, mostnotably in the first 1 to 2 hours postinjury, butgenerally reaches a plateau by 24 hours, andthen although remaining elevated above normalgradually declines over the next few days.19,21,29

s increases significantly in the microcirculationwithin and surrounding the burn wound and ishere the most important cause of edema. Thecapillary membrane becomes permeable tomany plasma proteins including albumin andsmall-to-moderate sized globulins. In the dermiss drops numerically from 0.9 (nearly impermeable)to 0.3 (highly permeable). This increase in capillarypermeability is most profound acutely and mayremain elevated for several days postburn. Theseverity and duration of the leak is directly propor-tional to the extent of the burn.19,25,29–31

Kf increases following a burn injury, whichmeans that fluid can more easily cross the capillary

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membrane into the interstitial space. Of particularimportance is that the compliance of the interstiti-um itself increases. This probably is related todestruction of the collagen framework andsurrounding matrix, which normally restricts fluidinflux. Furthermore, as edema progresses, hydra-tion of the matrix increases the compliancebecause the swelling mechanically disrupts bondsbetween various macromolecules. A self-perpetu-ating cycle is created in which edema leads tomore edema formation, allowing large increasesin interstitial volume with relatively littlecorresponding increase in hydrostaticpressure.19,29,32,33

Pcap – Pi, the hydrostatic pressure gradient,increases meaning that there is an increasedhydrostatic force moving fluid out of the vascularspace and into the interstitium. This is partlycaused by a small and transient increase in Pcap

immediately following the burn, but more impor-tantly by a profound (albeit transient) decrease inPi from its usual value of �2 to 12 mm Hg to aslow as �20 to �40 mm Hg. This is believed tooccur because the collagen and hyaluronic acidare held in the dermis in a dense, tightly packedcoiled configuration. Burn and inflammation-medi-ated collagen denaturation allows an unraveling ofthis framework and produces fragmentation of themolecules into osmotically active particles. Theend result is that, much like a compressed spongethat is allowed to expand, the interstitium drawsfluid into itself by creating a negative ‘‘sucking’’or ‘‘vacuum’’ force, lowering Pi and dramaticallyincreasing the hydrostatic gradient Pcap –Pi.

19,29,34 As fluid expands the interstitium, Pi

begins to rise again and returns to a slightly posi-tive value within a few hours. As described previ-ously, however, because of the increasedinterstitial compliance, interstitial pressures donot rise with this volume increase to the degreethat happens in the normal state.19

pp – pi, the osmotic pressure gradient, is nor-mally 10 to 12 mm Hg but begins to decreasefollowing burn injury, which means that there isless osmotic force to hold fluid within the intravas-cular space. An important force that normallyneutralizes the hydrostatic pressure gradient iseliminated. This occurs as a result of decreasingplasma protein concentration caused by leakageof protein across the now highly permeableplasma membrane (hence pp decreases), and bya gradual increase in pi as plasma proteins andother osmotically active particles accumulate inthe interstitium.19,28

To summarize, the following takes place withinand surrounding the burn wound. The capillarymembrane becomes highly permeable

immediately following the burn, allowing fluid andplasma proteins to move from the vascular spaceinto the interstitial space, reducing the colloidosmotic pressure gradient, which normally helpsto retain fluid within the vascular space. Simulta-neously, an increase in the hydrostatic pressuregradient, produced in part by a transient butpowerful ‘‘sucking’’ force, displaces fluid fromthe vascular space into the interstitium. Finally,breakdown of the collagen framework of the inter-stitium and progressive hydration of its matrix asedema develops make the interstitium morecompliant facilitating entry of even more fluid intothis space, perpetuating edema generation.

Alteration of Starling Forces in NonburnSoft Tissues

When the burn size approaches 25% to 30%TBSA or larger, edema in the unburned skin andsoft tissues develops.24 Acutely, within the firstfew hours postburn, there is an increase in capil-lary permeability (s), which may be caused bythe systemic dissemination of inflammatory medi-ators.35–37 The change in s is transient and capil-lary permeability soon returns to normal, butedema continues to develop in the nonburntissues for at least 24 to 36 hours postinjury. Themost important alteration is the loss of plasmacolloid osmotic pressure and resultant decreasein the colloid osmotic pressure gradient (pp – pi)as a consequence of the hypoproteinemic statethat develops with burns greater than or equal to25% to 30% TBSA. Correction of the hypoprotei-nemic state with infusions of albumin or plasmahinders the development of nonburn soft tissueedema.25,38

Hemodynamic Consequencesof the Fluid Shifts

The most important consequence of the afore-mentioned fluid shifts is a reduction in circulatingplasma volume. Cardiac output (CO) falls, largelybecause of hypovolemia and reduced preload,but interestingly in larger burns (R40% TBSA),an immediate fall in CO has been repeatedlyobserved before any measurable decrease in theplasma volume, suggesting that depressedmyocardial contractility plays a role. Earlier litera-ture suggested that an uncharacterized ‘‘myocar-dial depressant factor’’ was responsible,39–42 andit is now thought that inflammatory mediatorsfrom the burn wound, distributed systemically,are responsible.43,44 Further supporting the likeli-hood of direct myocardial depression is the factthat CO has been observed to remain temporarilydepressed despite restoration of plasma volume

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with fluid resuscitation. Simultaneous with theacute reductions in plasma volume and CO,systemic vascular resistance increases becauseof sympathetic-mediated peripheral vasoconstric-tion and the effects of increased viscosity of theblood because of hemoconcentration. The eleva-tion in systemic vascular resistance is an addi-tional factor that contributes to the acutedepression of CO.45 Organ perfusion, particularlyrenal blood flow, is compromised as a result ofthe hypovolemic state, depressed CO, and periph-eral vasoconstriction, especially if fluid resuscita-tion is delayed. As resuscitation proceeds, COslowly climbs back to normal and in patients withmajor burn injuries, a hyperdynamic picture withsupranormal CO develops by 36 to 72 hours post-burn as part of the hypermetabolic response.

The intended goal of fluid resuscitation is tore-expand the plasma volume, restore CO, andimprove organ and tissue perfusion. It should beevident from the foregoing discussion that crystal-loid resuscitation fluids, although necessary toachieve the goal of restoring tissue perfusion, arealso subject to the altered Starling forces and assuch, large amounts of the resuscitation fluidnecessarily end up as interstitial and cellularedema fluid.

CRYSTALLOID RESUSCITATION

In North America, resuscitation based on use ofcrystalloids during the first 24 hours postburn hasbeen the dominant strategy for several decades.Most clinicians continue to base early fluid resusci-tation on the Parkland formula for the initial 24-hourperiod (4 mL of Ringer’s lactate (RL) per kilogrambody weight per percent TBSA burn with half thevolume given in the first 8 hours postburn). Therationale behind the use of RL (Na 130 mEq/L,physiologic pH 7.4) and no colloid in the first24 hours is based on two observations. First, thefluid leaving the intravascular space, which thenaccumulates in the interstitial space as edema fluid,is isotonic relative to the plasma with a similar pHand ratio of sodium to potassium as plasma.7

Second, the acute increase in capillary perme-ability (s) within and around the burn wound allowsmost plasma proteins to leave the vascular spaceand enter the interstitium during the first 24 hours,so that the protein concentration of the edema fluidbegins to approach that of plasma.19,28

The Parkland formula seems to suggest thata fixed amount of 4 mL/kg/%TBSA burn shouldbe administered and that a static rate of infusionfollows a series of stepwise cuts at 8 and 24 hours(Fig. 3). The single most important principle in usingthe Parkland formula, however, is that it should be

used only as a guideline to determine an initialrate of fluid infusion. The resuscitation rate andvolume must be continually adjusted based onthe response of the patient (see Fig. 3). A secondimportant principle of Parkland-based crystalloidresuscitation, which is frequently ignored bymodern burn clinicians but which was emphasizedin two important consensus conferences,10,46,47 isthat resuscitation should use the least amount offluid (ie, somewhere between 2 and 4 mL/kg/%TBSA) necessary to achieve adequate UO andprevent early organ failure and avoid later compli-cations. What exactly qualifies as ‘‘adequate’’ UOis open to some debate. Unfortunately, in severalof Baxter’s publications on the Parkland formula,‘‘recommended’’ UO fluctuated between 50 and70 mL/h,9 50 and 100 mL/h,22 greater than 40 mL/h,9

and 40 to 70 mL/h.46 One question that has notbeen completely resolved is whether the desiredUO of 0.5 to 1 mL/kg/h should be based on actualbody weight or predicted body weight. The issueof what constitutes optimum UO is highly importantbecause more fluid delivery is needed to drive theUO to the higher end of any desired range, whichalso results in increased edema formation. Thebody mass index of the average North Americanhas been steadily increasing over the past severaldecades48 and one wonders if this may be partlyresponsible for fluid creep, as clinicians try toachieve higher and higher weight-based hourlyUO. Currently, some experts recommend mainte-nance of UO of 30 to 50 mL/h in adults and 1 to2 mL/kg/h in children weighing less than 30 kg,49

whereas current Practice Guidelines of the Amer-ican Burn Association advise maintenance of UOat approximately 0.5 to 1 mL/kg/h in adults and1 to 1.5 mL/kg/h in children.50

During the second 24-hour period postburn,Baxter22 recommended that 20% to 60% of thecalculated plasma volume be restored by adminis-tration of colloid, in the form of plasma. Additionalfluid in the form of dextrose and water would beused to maintain UO. The amount of colloidrequired varied between 0.3 and 0.5 mL/kg/%TBSA burn.46 Baxter22 argued that this amount issufficient to re-expand the plasma volume inmost patients where the capillary leak would besealed by 24 hours, but recognized that ina minority of patients colloid may not be effectiveuntil 36 hours postburn because of ongoing capil-lary leak between 24 and 36 hours postburn.22 Theprovision of colloid after 24 hours postburn isfrequently underemphasized in descriptions ofmodern crystalloid fluid resuscitation strategies.With the re-emergence of interest in use of colloidsas a fluid-sparing strategy to limit fluid creep (dis-cussed later), this often forgotten component of

Fig. 3. Chart showing hourly resuscitation data from a 40-year-old man weighing 100 kg with a 74% TBSA flameburn. The actual fluid volume delivered is consistently above the Parkland prediction, which theoretically suggestsa static infusion rate with a prescribed cut at 8 hours postburn (top panel). Note that the hourly infusion rate iscontinually adjusted to keep UO between 0.5 and 1 mL/kg/h (bottom panel). This patient survived.

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the Parkland formula may take on greater impor-tance in the future.

DIVERGENCEOFACTUAL AND PREDICTED FLUIDVOLUMES DURING CRYSTALLOID RESUSCITATIONPredictable Scenarios

In a variety of predictable situations, resuscitationvolumes are significantly greater than anticipatedby the Parkland formula. These situations includedelayed resuscitation,51 high voltage electricalburns, coincident alcohol intoxication,52 extensivedeep burns,14 advanced age,53 and the presenceof smoke inhalation injury.53–57 The increased fluidrequirements when burn injury is combined withinhalation injury have been well characterizedand repeatedly demonstrated among humanburn plus smoke inhalation patients to rangebetween 35% and 65% greater than burn injuryalone.54–57 In practice, however, this does notmean that a higher value than 4 mL/kg/%TBSAburn should be used to calculate the initial infusionrate. Rather, the clinician should initiate fluidsusing the Parkland formula, but should anticipategiving more fluid than predicted (again, titratedbased on the patient’s response), and importantly,not to reduce fluids to ‘‘run the patient dry’’ out ofconcern for the pulmonary injury. These patientsrequire increased volumes of crystalloid fluid toavoid burn shock.

Unpredictable Scenarios and Fluid Creep

The more pressing problem for the modern burnclinician is fluid creep, which is the unpredictabletrend toward provision of larger and larger resusci-tation fluid volumes to burn patients who do not fitinto the well-defined subgroups identified previ-ously. A number of recent studies have foundthat crystalloid fluid resuscitation volumes for theinitial 24 hours postburn among burn patientshave ranged between 4.8 and 6.7 mL/kg/%TBSA,13–18 in many instances independent ofthe presence of a documented inhalation injury.The consequences of this increased fluid adminis-tration are similarly well characterized, and includeairway swelling requiring prophylactic intubation58

(see Fig. 1), secondary ACS,59 soft tissue edemain the extremities necessitating more frequentescharotomies and even fasciotomies,58 elevatedintraocular pressures,60 and an overall increasedrisk of death.18

The development of intra-abdominal hyperten-sion (IAH) and the ACS deserve special mentionbecause these are perhaps the most dangerousand frequently reported consequences of fluidcreep in association with massive burn resuscita-tion (Fig. 4).59,61–64 The most recent ConsensusGuidelines define IAH as an intra-abdominal pres-sure (obtained by transduction of bladder pres-sure) greater than or equal to 12 mm Hg and

Fig. 4. A patient with 65% TBSA full-thickness burnsand smoke inhalation who developed ACS andrequired decompressive laparotomy. This patient didnot survive.

Fig. 5. Extension of abdominal escharotomies tocontrol rising intra-abdominal pressures. These es-charotomies may be extended further (dotted lines)in a ‘‘checkerboard pattern’’ as needed.

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ACS as an intra-abdominal pressure greater than20 mm Hg with evidence of new organ dysfunction(typically manifested as oliguria, impairedmechanical ventilation with high peak airway pres-sures, worsening metabolic acidemia, and hemo-dynamic instability).65 ACS is consideredsecondary when there is no demonstrable intra-abdominal pathology,65 as in the case of a burnwhere bowel and mesenteric edema andincreased peritoneal fluid are the cause of theraised intra-abdominal pressures. Left untreated,ACS is invariably fatal, and probably was thecause of early ‘‘death due resuscitation failure’’before formal recognition of the syndrome. Ivyand colleagues62 prospectively followed burnpatients with intra-abdominal pressure greaterthan 25 mm Hg and developed a score that indi-cated that cumulative resuscitation volumesgreater than or equal to 250 mL/kg were associ-ated with IAH and a high risk of ACS.62,66 Whencumulative volumes reach 250 mL/kg or moreintra-abdominal pressure measurements (bybladder pressure transduction) should be per-formed every 2 hours and conservative measuresto reduce intra-abdominal pressure should beconsidered.62,66 These include use of neu-romuscular relaxants and increased sedation inmechanically ventilated patients; extension of es-charotomies on any anterior trunk burns (Fig. 5);and possible judicious use of diuretics if adequateintravascular volume can be confirmed by place-ment of a pulmonary artery catheter, whichdemonstrates pulmonary capillary wedge pres-sures greater than 18 mm Hg.62,66,67 Studies ina limited number of patients have found that insome instances, IAH and possibly early ACS maybe reversed by the insertion of peritoneal dialysiscatheters to remove peritoneal fluid, but thisdoes not treat the edema of the intra-abdominal

tissues and organs, and with more severe ACS,particularly with massive burn injury, definitivetreatment by decompressive laparotomy maybe required.59,67,68 Mortality following surgicaldecompression for ACS is reported to be between50% and 100%.59,63,66,68

Why is fluid creep happening?One observation is that clinicians treating burnpatients do not devote adequate attention to thecareful titration (and in particular the downwardtitration) of fluids to keep UO within a tightlycontrolled range, ideally at the lower end of theaccepted range.69 In some of the studies thatdescribed resuscitation volumes in excess ofParkland predicted range, mean UOs during thefirst 24 hours postburn exceeded 1 mL/kg/h inmost patients.13,14,16,17 Similarly, Cancio andcolleagues15 from the US Army Burn Center foundthat in the face of high UO (>50 mL/h or >1 mL/kg/h)over 2 consecutive hours during burn resuscita-tion, the treating clinicians appropriately reducedthe RL infusion only 33% of the time. Finally,excessive fluid provision in the pre–burn centersetting by well-meaning emergency personnelmay be a source of excessive fluids. In one studyburn patients had received a mean of 2.5 L of RLwithin the mean delay of 2.8 hours between injuryand arrival to the burn center.14 Althoughadequate early fluid provision is important,aggressive fluid infusion is not necessarily better.Clinician inattention, however, cannot entirelyaccount for the phenomenon of fluid creep. Otherstudies that have reported 24-hour resuscitationvolumes in excess of 4 mL/kg/% TBSA alsoreported that the mean 24-hour UOs in these patientsfell within the range of 0.5 to 1 mL/kg/h,15,18

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suggesting that fluid creep may develop even withappropriate titration of the resuscitation.

Another consideration is that the original popu-lation of patients treated with the Parkland formulaand reported in Baxter’s original studies may notbe representative of current practice, wheregreater numbers of patients with larger and moreextensive burn injuries routinely survive resuscita-tion.69 In many of these massive injuries, resusci-tation volumes greatly exceed 4 mL/kg/% TBSA.Significant associations between both the burnsize15,17 and burn depth14 and an excessive resus-citation volume have been demonstrated in recentstudies. Volumes above the Baxter range may bethe necessary cost of successfully resuscitatinglarger and deeper burns.

The trend toward abandonment of colloids overthe past two or three decades may also havecontributed to the subtle advance of fluid creep.69

Baxter’s original approach included use of plasmaat 24 hours, and two well-conducted randomizedprospective studies both demonstrated that earlyuse of colloids significantly reduced 24-hourresuscitation volumes, compared with use of crys-talloids alone.70,71

An intriguing theory on fluid creep has beendescribed by Saffle,69 who suggests that fluidcreep may be a physiologically based phe-nomenon in which excessive fluid in the earlypostburn period, combined with the alteredderangements in the Starling forces describedpreviously, may perpetuate a self-repeatingcycle of edema-genesis and escalating volumerequirements. Under this theory, excessive fluidearly on could increase the capillary hydrostaticpressure (Pcap) and drive more and more fluidinto the interstitial space, causing edema, loos-ening interstitial structure, and increasing itscompliance, allowing more and more edema toform. Simultaneously, this process lowers theplasma colloid osmotic pressure (pp) allowingmore fluid flux out of the vascular space and re-sulting in a vicious cycle characterized by wors-ening edema formation and an escalating needfor more and more crystalloid resuscitation fluid.This might explain a paradoxic observation fromthe author’s institution that resuscitation volumesare relatively close to predicted during the first8 hours postinjury (where one expects capillaryleak to be most severe), but then severelydeviate above predicted during the second andthird 8-hour periods postburn.14

A final mechanism, referred to as ‘‘opioidcreep,’’ may also contribute to fluid creep.69,72

Sullivan and colleagues72 identified a correlationbetween elevated resuscitation volumes andincreased dosages of opioid analgesics at the

Harborview Burn Center in Seattle. Opiates dohave important cardiovascular effects, such ashypotension, which could lead to increased fluidadministration during acute burn resuscitation.As with the previously described mechanisms,opioid creep is likely not the sole cause but oneof several contributory factors.

END POINTS ANDMONITORING DURINGCRYSTALLOID RESUSCITATION

Hourly urine output is still the cornerstone ofmonitoring of burn resuscitation despite the emer-gence in the past decade of more sophisticatedapproaches, such as the use of malperfusionmarkers (arterial base deficit and serum lactate);cardiac index determinations; measurements ofoxygen delivery and uptake variables; and intratho-racic blood volume estimations. The fluid infusionrate should be adjusted to achieve a UO of 0.5 to1 mL/kg/h in adults and 1 to 1.5 mL/kg/h in chil-dren.50 It has never been specified whether thisshould be based on actual or predicted weight,but in heavier and obese patients, aiming for a UOat the lower end of the range seems to make senseto use the least amount of fluid possible.

The arterial base deficit and serum lactate arewell-recognized markers of tissue malperfusionthat have been used to monitor resuscitation intrauma and critically ill populations. More recently,several investigators have demonstrated thatthese are also important markers during burnresuscitation and that their elevation or failure tocorrect over time are associated with increasedmorbidity (eg, increased fluid requirements, multi-organ dysfunction, and acute respiratory distresssyndrome73,74) and predict increased mortality.75–77

Unfortunately, it is not known yet how to use thesemarkers to guide resuscitation, and more impor-tantly whether resuscitation directed at theircorrection improves outcome.

The use of invasive cardiovascular monitoringduring burn resuscitation has been investigatedby several groups.78–80 The principle is to usefluids and inotropes to optimize in a goal-directedfashion a variety of end points, such as serumlactate, base deficit, cardiac index, and oxygendelivery and uptake. Although one study foundthat a goal-directed resuscitation improvedsurvival,78 other studies have failed to show anyobvious benefit to this approach,79,80 and impor-tantly demonstrated that ‘‘optimization’’ of cardiacindex and oxygen uptake required liberal provisionof crystalloid fluid, well above Parkland predic-tions.79,80 It is noteworthy that nearly 40 yearsago Baxter and others45 observed that crystalloidresuscitation did not normalize preload, CO, or

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pH for at least 24 to 48 hours. One wonders ifattempts to normalize these variables moreaggressively and earlier in resuscitation by usinghigh fluid infusion volumes may be anothercontributory cause of fluid creep.69

COLLOID RESUSCITATION

Although original resuscitation strategies, such asthe Evans and Brooke formulas, provided colloidsduring the first 24 hours, concern about the lossof capillary membrane integrity and leakage ofdelivered proteins into the interstitial spaceprogressively led to avoidance of colloids in the first24-hour period and reliance on a pure crystalloidapproach for the first 24 hours. At the presenttime, burn clinicians generally fall into three groupswith respect to colloid provision: (1) some believe itshould not be used before 24 hours, because of theloss of capillary integrity, which could allow accu-mulation of the administered protein (and water)in the interstitium, particularly the lung;70 (2) othersadvocate immediate colloids (albumin) on the basisthat these help to maintain intravascular volume;4

and (3) a third group takes an intermediateapproach and gives colloids at 8 to 12 hours post-injury arguing that normal capillary permeability isrestored in nonburn soft tissues by 8 to 12 hoursand that hypoproteinemia is the major cause ofongoing edema formation at this time.25,38

Two randomized prospective studies havecompared crystalloids with early colloid in the first24 hours postburn. Goodwin and colleagues70 in1983 randomized adult burn patients to resuscita-tion with RL, or a 2.5% albumin in RL solution, bothtitrated to achieve a UO of 30 to 50 mL/h. Thealbumin-treated group achieved the desired UOend point and had significantly higher echocardi-ography-measured cardiac index, with significantlyless resuscitation fluid than the crystalloid-onlygroup. The albumin group, however, had signifi-cantly greater late lung water accumulation afterresuscitation. In a more recent study, O’Maraand colleagues71 randomized adult burn patientsto resuscitation with a RL infusion or to 2000 mLof RL infused over 24 hours combined with anadjustable infusion 75 mL/kg of fresh frozenplasma, with infusions in both groups titrated toachieve an hourly UO between 0.5 and 1 mL/kg/h. The colloid group required significantly lessresuscitation fluid to achieve the UO end point,which resulted in significantly lower peak intra-abdominal and airway pressures in that group,presumably on the basis of less edema formationin that group. From these two studies, it can besafely concluded that early colloid provisionreduces overall resuscitation volume requirements

and early edema formation. Whether this mighttranslate to other benefits, such as improvedsurvival, is unknown at this time. It is also impor-tant to point out that use of fresh frozen plasmaas the early colloid is not generally recommendedoutside of an approved research protocol,because this colloid is a limited and expensiveblood bank resource, and because of the potentialfor viral disease transmission and induction oftransfusion-related acute lung injury.81 Use of5% albumin is an acceptable alternative, and atthe author’s institution they begin an infusion of50 to 100 mL/h of 5% albumin at 8 to 12 hourspostburn in burns greater than 40% or as a formof ‘‘colloid rescue’’ when crystalloid volumes aredeviating significantly above predicted.

To a lesser extent, the use of nonprotein colloidsolutions, such as Dextran, Pentastarch, orHetastarch, in burn resuscitation has also beendescribed. Over two decades ago Demling andcolleagues,38 in an animal model, demonstratedthat burn resuscitation with Dextran 40 (low-molec-ular-weight Dextran) maintained hemodynamicvariables and UO with significantly less fluid andsignificantly less nonburn tissue edema, than withRL alone. This was caused by an increase inthe colloid osmotic pressure gradient by thelow-molecular-weight Dextran. Human studiesinvolving small numbers of patients suggest thatstarches are comparable volume expanders whencompared with albumin during the first 24 hoursof resuscitation.82 Until more data and experienceare accumulated with these substances, however,their routine use cannot be recommended.

HYPERTONIC SALINE RESUSCITATION

The appeal of HTS in burn resuscitation stemsfrom its ability to shift water from the intracellularspace into the extracellular compartment, and inso doing, expand the intravascular space. Theobvious benefits to the burn patient are the needfor less fluid administration, and less generationof tissue edema. Indeed, the pioneers of HTSburn resuscitation, Monafo and Moylan, demon-strated that hypertonic salt solutions wereeffective volume expanders that resulted inacceptable resuscitation with less fluid volumeand edema formation than when isotonic solutionswere used.83–85 Subsequent studies have mostlyconfirmed these early findings.86–89 A consensuson the most appropriate use of HTS during burnresuscitation has not been reached because ofthe wide variations in the timing (bolus versuscontinuous infusion), composition (HTS versusHTS plus colloid), and concentration of the hyper-tonic solutions that have been reported.86,88–91

Cartotto578

Hyperosmolarity and hypernatremia are ever-present dangers with use of this strategy, andserum sodium concentrations must be frequentlyand carefully monitored to avoid complications,such as organ failure and death related either toexcessive or prolonged hyperosmolarity, or toorapid correction of the hyperosmolar state. Serumsodium levels should be maintained at less than160 mEq/L.49 The ultimate dangers in HTS resus-citation are described in the study by Huang andcolleagues,92 who reported a fourfold increase inthe incidence of acute renal failure associatedwith HTS resuscitation. Marked and sustainedelevations in serum sodium were the hallmarks ofpatients who developed acute renal failure in thatstudy. Current practice guidelines of the AmericanBurn Association recommend that HTS resuscita-tion should be used by experienced burn cliniciansand should be accompanied by meticulous moni-toring of serum sodium concentrations.

PRACTICAL POINTERS FOR OPTIMIZING BURNRESUSCITATION ANDMINIMIZING FLUID CREEPPay Close Attention to Pre–burn CenterFluid Administration

Overzealous fluid administration combined withoverestimation of burn size by prehospital andemergency room personnel can contribute to fluidcreep (Table 1). It is incumbent on the plasticsurgeon who is involved in the early care of the

Table1Summary of practical pointers for the plastic surgeon invwithmajor burn injuries

Principle Intervention

When to resuscitate? % TBSA sec

Where to start? Calculate 4in the firs

From the tiMust includ

Attention to pre–burn center fluids Ensure corrReview form

Titration Use formulaMonitor UOConsider boReduce infu

(whicheve

Colloids Consider 5%120%–20

Monitor edema Repetitive band tidal

Bladder pre>200–250

Abbreviations: TBSA, total body surface area; UO, urinary out

burn patient carefully to review the extent of burnwith first providers. Similarly, repeated communi-cation with the emergency room to review fluidinfusion rates and UO is important when transferto a burn center is delayed beyond a few hours.

Titrate, Titrate, Titrate

Rigid adherence to a fluid infusion rate prescribedby a formula is potentially harmful. Rather, theclinician should continually adjust the infusionrate based on the patient’s response. Practically,this is based on evaluation of the UO at 1- to 2-hour intervals. A protocol, such as that describedby Saffle,69 is one of several ways to achieve thisgoal. In this strategy, an hour of UO less than15 mL calls for an increase in the infusion rate by20% or 200 mL/h, whichever is greater; an hourwith UO 15 to 30 mL gets an increase of 10% or100 mL/h, whichever is greater; and hour withUO 30 to 50 mL prompts no change in the infusionrate. Conversely, for UO greater than 50 mL/h theinfusion rate for the next hour is decreased by 10%or 100 mL/h, whichever is greater. Within thisparticular protocol, persistent oliguria or esca-lating fluid infusion rates are managed by institu-tion of albumin, described next.

Contemplate Colloids

Colloids do seem to reduce the overall volumerequirements compared with use of crystalloid

olved in early resuscitation of a patient

s

ond- or third-degree burns are R20%

mL/kg/%TBSA, with half this volume administeredt 8 hours

me of injurye any fluids already administered

ect TBSA estimationula, infusion rate, urinary output regularly

s to determine starting infusion rate onlyq 1–2 h

lus or increase in infusion rate for oliguriasion by approximately 10% or 100 mL/hr is greater) for UO >50 mL/h

albumin when cumulative fluids reach0% of predicted

edside examination of edema, airway pressure,volume trendsssure measurements when cumulative fluidsmL/kg or >500 mL/h

put.

Fluid Resuscitation 579

alone.70,71 Colloids may be instituted according tothe original recommendations of the Parklandformula by administering approximately 0.3 to0.5 mL/kg/%TBSA of 5% albumin during thesecond 24 hours of resuscitation. One of myapproach is to administer colloids as a ‘‘rescue’’technique when crystalloid requirements becomeexcessive. Yowler and Fratienne93 start albuminat 12 hours postburn if fluid needs are greaterthan 120% predicted; Saffle’s69 protocol calls foralbumin for persisting oliguria or infusion ratesmore than twice the calculated rate for greaterthan 2 hours; and Chung and colleagues94 recom-mend 5% albumin if a patient, at 12 to 18 hourspostburn, has a projected 24-hour requirementthat exceeds 6 mL/kg/%TBSA.

Monitor Edema, Especiallyin the Abdominal Compartment

Serial bedside assessments of the evolution of thepatient’s soft tissue edema, particularly in theabdominal compartment, combined with regularmeasurement of bladder pressures are importantadjuncts when burns are extensive; when oliguriapersists; or when volume requirements becomeexcessive (eg, cumulative volume >200–250 mL/kgor >500 mL/h).

REFERENCES

1. Pruitt BA. Protection from excessive resuscitation:

pushing the pendulum back. J Trauma 2000;49:

567–8.

2. Underhill F. The significance of anhydremia in exten-

sive superficial burns. JAMA 1930;95:852–7.

3. Cope O, Moore F. The redistribution of body water

and the fluid therapy of the burned patient. Ann

Surg 1947;126:1010–45.

4. Evans EI, Purnell OJ, Robinett PW, et al. Fluid and

electrolyte requirements in severe burns. Ann Surg

1952;135:804–17.

5. Reiss E, Stirman JA, Artz CP, et al. Fluid and electro-

lyte balance in burns. JAMA 1953;152:1309–13.

6. Moyer CA, Margraf HW, Monafo WW. Burn shock

and extravascular sodium deficiency: treatment

with Ringers solution with lactate. Arch Surg 1965;

90:799–811.

7. Baxter CR, Shires T. Physiological response to crys-

talloid resuscitation of severe burns. Ann N Y Acad

Sci 1968;150:874–94.

8. Baxter CR, Marvin J, Curreri PW. Fluid and electro-

lyte therapy of burn shock. Heart Lung 1973;2:

707–13.

9. Baxter CR. Problems and complications of burn shock

resuscitation. Surg Clin North Am 1978;58:1313–22.

10. Baxter CR. Guidelines for fluid resuscitation.

J Trauma 1981;21:687–9.

11. Tremblay R, Ethier J, Querin S, et al. Veno-venous

continuous renal replacement therapy for burned

patients with acute renal failure. Burns 2000;26:

638–43.

12. Chrysopoulo MT, Jeschke M, Dziewulski P, et al.

Acute renal dysfunction in severely burned adults.

J Trauma 1999;46:141–4.

13. Engrav LH, Colescott PL, Kemalyan N, et al. A

biopsy of the use of the Baxter formula to resuscitate

burns or do we do it like Charlie did? J Burn Care

Rehabil 2000;21:91–5.

14. Cartotto R, Innes M, Musgrave MA, et al. How well

does the Parkland formula estimate actual fluid

resuscitation volumes? J Burn Care Rehabil 2002;

23:258–65.

15. Cancio L, Chavez S, Alvarado-Ortega M, et al. Pre-

dicting increased fluid requirements during the

resuscitation of thermally injured patients. J Trauma

2004;56:404–14.

16. Friedrich JB, Sullivan SR, Engrav LH, et al. Is supra-

Baxter resuscitation in burn patients a new phenom-

enon? Burns 2004;30:464–6.

17. Klein MB, Hayden D, Elson C, et al. The association

between fluid administration and outcome following

major burn: a multicenter study. Ann Surg 2007;

245:622–8.

18. Blumetti J, Hunt JL, Arnoldo BD, et al. The Parkland

formula under fire: is the criticism justified? J Burn

Care Res 2008;29:180–6.

19. Demling RH. The burn edema process: current

concepts. J Burn Care Res 2005;26:207–27.

20. Brouhard BH, Carvajal HF, Linares HA. Burn edema

and protein leakage in the rat: relationship to size of

injury. Microvasc Res 1978;15:221–8.

21. Carvajal HF, Linares HA, Brouhard BH. Relationship

of burn size to vascular permeability changes in

rats. Surg Gynecol Obstet 1979;149:193–202.

22. Baxter CR. Fluid volume and electrolyte changes in

the early post burn period. Clin Plast Surg 1974;1:

693–709.

23. Evans JA, Darlington DN, Gann DS. A circulating

factor mediates cell depolarization in hemorrhagic

shock. Ann Surg 1991;213:549–57.

24. Kramer GC, Lund T, Herndon DN. Pathophysiology

of burn shock and burn edema. In: Herndon DN,

editor. Total burn care. 2nd edition. Philadelphia:

Saunders Co; 2003. p. 78–87.

25. Demling RH, Kramer GC, Harms B. Role of thermal

injury induced hypoproteinemia on fluid flux and

protein permeability in burned and nonburned

tissue. Surgery 1984;95:136–44.

26. Starling E. On the absorption of fluids from the

connective tissue spaces. J Physiol 1896;19:

312–26.

27. Guyton AC, Coleman TG. Regulation of interstitial

fluid volume and pressure. Ann N Y Acad Sci

1968;150:537–47.

Cartotto580

28. Harms BA, Kramer GC, Bodai BI, et al. Effect of hy-

poproteinemia on pulmonary and soft tissue edema

formation. Crit Care Med 1981;9:503–8.

29. Lund T, Onarkeim H, Reed R. Pathogenesis of

edema formation in burn injuries. World J Surg

1992;16:2–9.

30. Cope O, Moore F. A study of capillary permeability in

experimental burns and burn shock using radioactive

dyes in blood and lymph. J Clin Invest 1944;23:241–9.

31. Bert J, Bowen B, Reed R, et al. Microvascular

exchange during burn injury: fluid resuscitation

model. Circ Shock 1991;37:285–97.

32. Granger HJ. Role of the interstitial matrix and

lymphatic pump in regulation of transcapillary fluid

balance. Microvasc Res 1979;18:209–16.

33. Leape L. Initial changes in burns: tissue changes in

burned and unburned skin of rhesus monkeys.

J Trauma 1970;10:488–92.

34. Lund T, Wiig H, Reed R, et al. A new mechanism for

edema formation: strongly negative interstitial fluid

pressure causes rapid fluid flow into thermally

injured skin. Acta Physiol Scand 1987;129:433–5.

35. Arturson G, Jakobsson OR. Oedema measurements

in a standard burn model. Burns 1985;1:1–7.

36. Arturson G. Microvascular permeability to macro-

molecules in thermal injury. Acta Physiol Scand

1979;463:111–22.

37. Harms B, Kramer GC, Bodai B, et al. Microvascular

fluid and protein flux in pulmonary and systemic

circulations after thermal injury. Microvasc Res

1982;23:77–86.

38. Demling RH, Kramer GC, Gunther R, et al. Effect of

nonprotein colloid on postburn edema formation in

soft tissue and lungs. Surgery 1984;95:593–602.

39. Baxter CR, Cook WA, Shires GT. Serum myocardial

depressant factor of burn shock. Surg Forum 1966;

17:1–3.

40. Hilton JG, Marullo DS. Effects of thermal trauma on

cardiac force of contraction. Burns Incl Therm Inj

1986;12:167–71.

41. Papp A, Uusaro A, Parvianen I, et al. Myocardial

function and hemodynamics in extensive burn

trauma: evaluation by clinical signs, invasive

monitoring, echocardiography, and cytokine

concentrations. A prospective clinical study. Acta

Anesthesiol Scand 2003;47:1257–63.

42. Adams HR, Baxter CR, Izenberg SD. Decreased

contractility and compliance of the left ventricle as

complications of thermal trauma. Am Heart J 1984;

108:1477–87.

43. Horton J, Maass D, White DJ, et al. Effect of aspira-

tion pneumonia: induced sepsis on post burn

cardiac inflammation and function in mice. Surg

Infect (Larchmt) 2006;7:123–35.

44. Huang YS, Yang ZC, Yan BG, et al. Pathogenesis of

early cardiac myocyte damage after severe burns.

J Trauma 1999;46:428–32.

45. Pruitt BA, Mason AD, Moncrief JA. Hemodynamic

changes in the early postburn patient: the influence

of fluid administration and of a vasodilator (hydral-

azine). J Trauma 1971;11:36–46.

46. Baxter CR. Fluid resuscitation, burn percentage,

and physiologic age. J Trauma 1979;19:864–5.

47. Pruitt BA. Fluid resuscitation for extensively burned

patients. J Trauma 1981;21:690–2.

48. Ford ES, Zhao G, Li C, et al. Trends in obesity and

abdominal obesity among hypertensive and non-

hypertensive adults in the United States. Am J

Hypertens 2008;21:1124–8.

49. Warden GD. Fluid resuscitation and early manage-

ment. In: Herndon DN, editor. Total burn care. 3rd

edition. Philadelphia: Saunders Elsevier Inc; 2007.

p. 107–18.

50. Pham TN, Cancio L, Gibran NS. American Burn

Association practice guidelines: burn shock resusci-

tation. J Burn Care Res 2008;29:257–66.

51. Wolf SE, Rose JK, Desai MH, et al. Mortality determi-

nants in massive pediatric burns: an analysis of 103

children with R80% TBSA burns (R70% full thick-

ness). Ann Surg 1997;225:554–65.

52. Warner P, Connolly JP, Gibran NS, et al. The meth-

amphetamine burn patient. J Burn Care Rehabil

2003;24:275–8.

53. Pruitt BA. Fluid and electrolyte replacement in the

burned patient. Surg Clin North Am 1978;58:

1291–311.

54. Dai NT, Chen TM, Cheng TY, et al. The comparison

of early fluid therapy in extensive flame burns

between inhalation and non inhalation injury. Burns

1998;24:671–5.

55. Darling GE, Keresteci MA, Ibanez D, et al. Pulmo-

nary complications in inhalation injuries with associ-

ated cutaneous burns. J Trauma 1996;40:83–9.

56. Herndon DN, Barrow RE, Linares HA, et al. Inhala-

tion injury in burned patients: effects and treatment.

Burns Incl Therm Inj 1988;14:349–56.

57. Navar PD, Saffle JR, Warden GD. Effect of inhalation

injury on fluid resuscitation requirements after

thermal injury. Am J Surg 1985;150:716–20.

58. Zak AL, Harrington DL, Barillo DJ, et al. Acute respi-

ratory failure that complicates the resuscitation of

pediatric patients with scald injuries. J Burn Care

Rehabil 1999;20:391–9.

59. Hobson KG, Young KM, Ciraulo A, et al. Release of

abdominal compartment syndrome improves

survival in patients with burn injury. J Trauma 2002;

53:1129–34.

60. Sullivan SR, Ahmadi AJ, Singh CN, et al. Elevated

orbital pressure: another untoward effect of massive

resuscitation after burn injury. J Trauma 2006;60:

72–6.

61. Greenhalgh DG, Warden GD. The importance of in-

traabdominal pressure measurements in burned

children. J Trauma 1994;36:685–90.

Fluid Resuscitation 581

62. Ivy ME, Possenti PP, Kepros J, et al. Abdominal

compartment syndrome in patients with burns.

J Burn Care Rehabil 1999;20:351–3.

63. Oda J, Ueyama M, Yamashita K, et al. Effects of

escharotomy as abdominal decompression on

cardiopulmonary function and visceral perfusion in

abdominal compartment syndrome with burn

patients. J Trauma 2005;59:369–74.

64. Jensen AR, Hughes WB, Grewal H. Secondary

abdominal compartment syndrome in children with

burns and trauma: a potentially lethal combination.

J Burn Care Res 2006;27:242–6.

65. Malbrain ML, Cheatham ML, Kirkpatrick A, et al.

Results from the international conference of experts

on intra-abdominal hypertension and abdominal

compartment syndrome. 1. Definitions. Intensive

Care Med 2006;32:1722–32.

66. Ivy ME, Atweh NA, Palmer J, et al. Intra-abdominal

hypertension and abdominal compartment syndrome

in burn patients. J Trauma 2000;49:387–91.

67. Hershberger RC, Hunt JL, Arnoldo BD, et al.

Abdominal compartment syndrome in the severely

burned patient. J Burn Care Res 2007;28:708–14.

68. Latenser BA, Kowal-Vern A, Kimball D, et al. A pilot

study comparing percutaneous decompression with

decompressive laparotomy for acute abdominal

compartment syndrome. J Burn Care Rehabil

2002;23:190–5.

69. Saffle JR. The phenomenon of fluid creep in acute

burn resuscitation. J Burn Care Res 2007;28:

382–95.

70. Goodwin C, Dorethy J, Lam V, et al. Randomized

trial of efficacy of crystalloid and colloid resuscita-

tion on hemodynamic response and lung water

following thermal injury. Ann Surg 1983;197:520–8.

71. O’Mara MS, Slater H, Goldfarb W, et al. A prospec-

tive randomized evaluation of intra-abdominal pres-

sures with crystalloid and colloid resuscitation in

burn patients. J Trauma 2005;58:1011–8.

72. Sullivan SR, Freidrich JB, Engrav LH. Opioid creep

is real and may be the cause of fluid creep. Burns

2004;30:583–90.

73. Kaups KL, Davis JW, Dominic WJ, et al. Base deficit as

an indicator of resuscitation needs in patients with

burn injuries. J Burn Care Rehabil 1998;19:346–8.

74. Cartotto R, Choi J, Gomez M, et al. A prospective

study on the implication of a base deficit during fluid

resuscitation. J Burn Care Rehabil 2003;24:75–83.

75. Cochrane A, Edelman LS, Saffle JR, et al. The relation-

ship of serum lactate and base deficit in burn patients

to mortality. J Burn Care Res 2007;28:231–40.

76. Jeng JC, Jablonski K, Bridgeman A, et al. Serum

lactate not base deficit rapidly predicts survival after

major burns. Burns 2002;28:161–6.

77. Cancio LC, Galvez E, Turner CE, et al. Base deficit

and alveolar-arterial gradient during resuscitation

contribute independently but modestly to the

prediction of mortality after burn injury. J Burn Care

Res 2006;27:289–96 [discussion: 296–7].

78. Schiller WR, Bay CR, Garren RL, et al. Hyperdynamic

resuscitation improves survival in patients with life

threatening burns. J Burn Care Rehabil 1997;18:10–6.

79. Barton RG, Saffle JR, Morris SE. Resuscitation of

thermally injured patients with oxygen transport

criteria as goals of therapy. J Burn Care Rehabil

1997;18:1–9.

80. Holm C, Mayr M, Tegeler J, et al. A clinical random-

ized study on the effects of invasive monitoring on

burn shock resuscitation. Burns 2004;30:798–807.

81. Higgins S, Fowler R, Callum J, et al. Transfusion

related acute lung injury in patients with burns.

J Burn Care Res 2007;28:57–64.

82. Waters LM, Christensen MA, Sato RM. Hetastarch:

an alternative colloid in burn shock management.

J Burn Care Rehabil 1989;10:11–5.

83. Monafo WW, Halverson JD, Schechtman K. The role of

concentrated sodium solutions in the resuscitation of

patients with severe burns. Surgery 1984;95:129–34.

84. Monafo WW. The treatment of burn shock by the

intravenous and oral administration of hypertonic

lactated saline. J Trauma 1970;10:575–86.

85. Moylan JA, Reckler JM, Mason AD. Resuscitation

with hypertonic lactate saline in thermal injury.

Am J Surg 1973;125:580–4.

86. Caldwell FT, Bowser BH. Critical evaluation of hyper-

tonic and hypotonic solutions to resuscitate severely

burned children. Ann Surg 1979;189:546–52.

87. Jelenko C, Williams JB, Wheeler ML, et al. Studies in

shock and resuscitation. I: use of a hypertonic

albumin containing fluid demand regimen(HALFD)

in resuscitation. Crit Care Med 1979;7:157–65.

88. Shimazaki H, Yukioka T, Matuda H. Fluid distribution

and pulmonary dysfunction following burn shock.

J Trauma 1991;31:623–8.

89. Oda J, Ueyama M, Yamashita K, et al. Hypertonic

lactated saline resuscitation reduces the risk of

abdominal compartment syndrome in severely

burned patients. J Trauma 2006;60:64–71.

90. Elgjo GI, Traber DL, Hawkins HK, et al. Burn resus-

citation with two doses of 4 ml/kg hypertonic saline

dextran provides sustained fluid sparing: a 48 hour

prospective study in conscious sheep. J Trauma

2000;49:251–65.

91. Milner SM, Kinsky MP, Guha C, et al. A comparison of

two different 2400 mOsm solutions for resuscitation of

major burns. J Burn Care Rehabil 1997;18:109–15.

92. Huang PP, Stucky FS, Dimick AR, et al. Hypertonic

sodium resuscitation is associated with renal failure

and death. Ann Surg 1995;221:543–7.

93. Yowler CJ, Fratienne RB. Current status of burn

resuscitation. Clin Plast Surg 2000;27:1–10.

94. Chung KK, Blackbourne LH, Wolf SE, et al. Evolution

of burn resuscitation in operation Iraqi Freedom.

J Burn Care Res 2006;27:606–11.