What’s New in CriticalCare of the Burn - InjuredPatient?

Tina L. Palmieri, MD, FACS, FCCMa,b,*

KEYWORDS� Burns � Sepsis � Inhalation injury � Critical care� Glycemic control

Mortality after burn injury has decreased markedly (ARDS).4 The risk for mortality from ALI and ARDS

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in the past 30 years. Survival after burn injury tomore than 90% of the total body surface area iscommon in children, with some authors maintain-ing that virtually all children with burn injury shouldbe resuscitated.1 Unfortunately, the improvementin survival does not apply to all age groups:survival in the elderly burn patient remains prob-lematic. The increases in survival after burn injuryhave been linked, in part, to a variety of woundtreatment modalities, including early excision andgrafting, cultured epithelial autografting, and theinstitution of broad-spectrum topical antimicrobialtherapy.2,3 Advances in critical care management,particularly with respect to ventilator manage-ment, resuscitation, and sepsis management,have also contributed to the improved survivalafter burn injury. This article describes theadvances in critical care management that havecontributed to the decline in mortality in burnpatients.

ADVANCES IN VENTILATORMANAGEMENT

Mechanical ventilation is frequently required aftermajor burn injury, especially when the patient hasconcomitant inhalation injury. The term ‘‘acutelung injury’’ (ALI) is used to designate the acuteonset of impaired oxygen exchange that resultsfrom lung injury, and the condition is characterizedby a PaO2/FiO2 ratio of less than 300. Severecases of ALI, in which this ratio is less than 200,are termed ‘‘acute respiratory distress syndrome’’

a Shriners Hospital for Children Northern California, 2495817, USAb University of California Davis, Medial Center, 2315 Sto* Corresponding author. University of California Davis, MCA 95817, USA.E-mail address: tina.palmieri@ucdmc.ucdavis.edu

Clin Plastic Surg 36 (2009) 607–615doi:10.1016/j.cps.2009.05.0120094-1298/09/$ – see front matter ª 2009 Elsevier Inc. All

approaches 40% to 50%.5 This mortality may bedirectly due to respiratory failure and hypoxia, orit may result from associated multisystem organfailure or ventilator-associated pneumonia. Newstrategies for mechanical ventilation are currentlybeing used to support burn patients who haverespiratory insufficiency, ALI, and ARDS. Thesestrategies include changes in traditional mechan-ical ventilation paradigms (such as the use oflow-tidal-volume ventilation) and the use of alter-native modes of ventilation.

Low-tidal-volume Ventilation

ALI and ARDS are caused by burn injury, sepsis,pancreatitis, and drug toxicity, and they are alsopresent in inflammatory states. ALI and ARDSare characterized by diffuse alveolar damage,with associated increases in capillary perialvolarpermeability. Protein-rich fluid is transmitted fromthe intravascular to the extravascular spaces andalveoli. This results in increases in cytokinerelease, the accumulation of macrophages andneutrophils in the alveolar-arteriolar interstitium,and decreases in surfactant production.6,7 All ofthese factors combine to result in airway damageand alveolar collapse.

Endotracheal intubation and mechanical ventila-tion are often necessary to support the patient whohas burn or inhalation injury with ALI and ARDS.Twenty years ago, the goal of ventilatory supportwas normalization of arterial blood gases (ie,

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a pH as close as possible to 7.4, pCO2 at 35–45mm Hg, and oxygen saturation greater than95%). This was accomplished using high pres-sures, inspired oxygen concentration, and minuteventilation delivered by volume-controlled ventila-tors. Tidal volumes of 10 to 15 mL/kg were thestandard, rationalized by the need for increasedrecruitment of collapsed alveoli.

These traditional ventilator-management strate-gies were challenged in several prospective,randomized trials. Reports of ventilator-inducedlung injury (VILI), associated with hyperinflation ofnormal regions of aerated lung due to high tidalvolumes began to appear. Overexpansion ofnormal alveoli leads to high transpulmonary pres-sures in aerated regions, making them susceptibleto direct physical damage. Data from animalstudies resulted in the recommendation to reduceplateau pressures to 35 mm Hg to lessen the contri-bution of VILI to the altered physiology of ALI andARDS. Peak transpulmonary pressure reductionwas accomplished by increasing positive end-expiratory pressure and decreasing tidal volume.The subsequent reduction in minute ventilation re-sulted in hypercapnia, which became popularlyknown as permissive hypercapnia.8 A series of clin-ical trials and a review by the Cochrane AnesthesiaReview group demonstrated that mortality could bedecreased in patients who had ALI and ARDS withthe use of tidal volumes of 6 mL/kg of ideal bodyweight.9–14 These protective effects were accom-plished using tidal volumes of less than 7 mL/kgof measured body weight and plateau pressuresof less than 31 cm of water.12,13,15 The reductionsin mortality and the duration of mechanical ventila-tion correlated directly with the magnitude of differ-ence in tidal volume between the control andtreatment groups. The two studies showing thehighest protective value of low-tidal-volume venti-lation10,11 calculated the delivered tidal volumebased on ideal, rather than measured, patientweight, suggesting that ventilator management inpatients who have ALI and ARDS should be guidednot by the actual weight, but by the ideal bodyweight. This is an important consideration inpatients who have a major burn injury becausethey often have vast increases in body weight dueto massive fluid resuscitation. However, thisstrategy is not without risk. Adverse effects ofa low-pressure ventilation strategy includeincreased intracranial pressure, decreasedmyocardial contractility, reductions in renal bloodflow, and pulmonary hypertension. However,multiple studies have shown that modest permis-sive hypercapnia is safe.16–18

Low-pressure ventilation should be consideredfor burn patients who have severe ALI and ARDS

because its use may decrease the incidence ofVILI and improve overall survival. However, giventhat this strategy has not been assessed ina prospective randomized trial in patients whohave burn injury, care must be taken in the applica-tion and monitoring this type of mechanical venti-lation in patients who have burn injury. The useof this ventilator strategy should not replace theuse of escharotomy for patients who have chestwall compartment syndrome, and care needs tobe taken to guard against airway obstruction inpatients who have inhalation injury.

New Methods of Mechanical Ventilation

Several nonconventional modes of ventilationhave been proposed for the treatment of severeARDS in patients who have burn injury, includingairway pressure release ventilation (APRV) andhigh-frequency oscillatory ventilation. Both ofthese methods use lower tidal volumes and aredesigned primarily to improve oxygenation.Although both methods have shown promise,neither has been extensively tested in patientswho have burn injury.

APRV, which was first described in 1987, isa time-triggered, pressure-limited, and time-cycled mode of ventilation that uses two differentlevels of airway pressures (high and low) overtwo different time periods (high and low).19 Inessence, APRV involves the maintenance ofa high, continuous, positive airway pressure thatintermittently time-cycles to a lower airway pres-sure. APRV is designed to optimize and maintainairway recruitment throughout the respiratorycycle by maintaining a higher mean airway pres-sure despite using lower tidal volumes and endexpiratory pressures than other forms of ventila-tion.20,21 The key to the successful use of APRVis to set the high pressure just a bit higher thanthe alveolar closing pressure, which allows alve-olar recruitment without alveolar collapse. Alveolarrecruitment is maintained during the inflationphase. The release phase, which is relatively short,allows for passive exhalation and ventilation.22

Oxygenation is achieved, with increases in inspira-tory pressure and time.

APRV thus allows for spontaneous breathingwhile decreasing the work of breathing and theneed for sedation. These salutary effects alsocan potentially minimize the impact of VILI andimprove hemodynamic parameters. Studies ofAPRV have been restricted primarily to cases ofARDS, and there are few reports of its use forpatients who have burns. Two randomized,controlled trials have been performed to assessAPRV, with variable results.23,24 Although neither

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study demonstrated differences in mortality orlength of stay, one study of trauma patients re-ported lower end-inflation pressures, improvedoxygenation, decreased ventilator duration, anddecreased ICU stay in the APRV group comparedwith the pressure control ventilation group.Caution must be exercised before using APRV,however, because it theoretically could result inlung overinflation and injury.

High-frequency Oscillatory Ventilation

High-frequency oscillatory ventilation (HFOV),which has been used for decades in neonatalICUs, is still under investigation for use in adultswho have ARDS. HFOV, like APRV, improvesoxygenation by maintaining elevated mean airwaypressure to recruit alveoli.25–28 It differs from volu-metric diffusive ventilation, the current standard ofcare for inhalation injury, in its use of higherfrequencies and time cycling. To achieve airwayrecruitment and improved oxygenation, HFOVuses extremely small tidal volumes (1–2 mL/kg)at high frequencies (3–15 Hz), as opposed tofrequencies of 300 to 600 Hz used in volumetricdiffusive ventilation. The result is the generationof sustained mean airway pressures of 30 to40 cm H2O. Oxygenation and ventilation areessentially uncoupled and can be controlledindependently.

HFOV has been shown to decrease VILI inanimal models by limiting alveolar stretch andavoiding atelectrauma, which is caused by therepeated opening and collapse of alveoli.29–33

The sustained recruitment of alveoli results inimproved oxygenation. HFOV has been used inadults primarily as a rescue mode of ventilationin cases of severe ARDS in different scenarios,including burn injury.34–39 To date, two random-ized, prospective trials have found no differencein outcomes between the use of HFOV andconventional mechanical ventilation; however,a current randomized, prospective trial isunderway and should define the use of HFOV incases of severe ARDS.40,41 One of the potentialmajor limitations of HFOV is difficulties with venti-lation and severe respiratory acidosis due toincreases in pCO2.

Although both APRV and HFOV are promisingmodalities for use in burn patients who haveARDS and ALI, neither has been rigorously studiedin a prospective, randomized fashion in patientswho have burns. Likewise, the ability to decreasethe incidence of volutrauma by reducing tidalvolumes during mechanical ventilation has notbeen thoroughly evaluated in patients who haveburn and inhalation injury. However, low-tidal-volume

ventilation has become the standard of care formechanical ventilation in patients who have ARDSand ALI.

RESUSCITATION AND FLUID MANAGEMENT

One of the greatest advances in burn treatment inthe twentieth century was the development andadoption of guidelines for burn resuscitation. Fluidestimation formulas, such as the Parkland formula,which allow for the adjustment of intravenous fluidadministration based on urine output, providedclinicians with easily identifiable endpoints ofresuscitation. Patients who had major burn injurywere seldom dying from underresuscitation.However, issues related to overresuscitationbegan to develop. ‘‘Fluid creep,’’ the term usedto describe the use of excessive intravenous fluidduring resuscitation, is being increasinglydescribed in the literature.42–45 Abdominalcompartment syndrome, considered by some tobe a consequence of excessive resuscitation,also is being increasingly documented in the liter-ature.46–49

Perhaps one of the most important issues inburn resuscitation is that the optimal measurableendpoint of resuscitation remains poorly defined.Studies attempting to generate variables predic-tive of resuscitation nonresponders have beenunsuccessful, and no single formula accuratelypredicts the fluid resuscitation needs for allpatients during burn shock.50 This lack of clarityis caused by the many confounding factorssurrounding burn injury, such as burn depth, inha-lation injury, associated injuries, age, delays inresuscitation, the need for escharotomies or fas-ciotomies, and the use of alcohol or drugs. Ideally,fluid resuscitation should be adjusted based onphysiologic endpoints. To date, urine output hasbeen the most commonly used endpoint, althoughthe value of using urine output to adjust fluid ratesduring burn shock has been challenged.51

In recent years, the use of invasive monitoringmethods, such as central venous pressure moni-toring or the pulmonary artery catheter, has beenpopularized, especially in the elderly, but recentreports raise questions about the utility of thepulmonary artery catheter in critically illpatients.52–55 Even central venous pressure hasbeen shown to be influenced more by intra-abdominal pressures than actual right atrialpressure.56

Thus, although the pulmonary artery catheterand central venous pressure provide additionalinformation regarding heart function, studies failedto demonstrate improved survival with their use.

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New invasive monitors continue to be devel-oped in an attempt to improve outcomes. Clini-cians can now continuously measure mixedvenous oxygenation, intrathoracic blood volume,total blood volume index, and extravascular lungwater using specialized thermodilution tech-niques.54,57 Pulse contour analysis, transesopha-geal echocardiography, partial carbon dioxiderebreathing, and impedance electrocardiographyare all recently developed techniques that areused to estimate cardiac output.58–61 Althoughthese techniques show great promise, their utilityin burn resuscitation remains unclear. Finally,tissue perfusion monitors, such as gastric tonom-eters or devices that measure oxygen and carbondioxide saturations in the subcutaneous tissues,have not been shown to improve resuscitation inburn patients. These techniques demonstrate lowperfusion capabilities despite other signs ofproviding adequate resuscitation and may actuallylead to overresuscitation.62,63

Blood Transfusion

Each year in the United States, more than $3 billionare spent on blood transfusions, with approxi-mately 25% of critically ill patients receiving atleast one blood transfusion to treat anemia.64–66

Although critically ill patients may be predisposedto the adverse effects of anemia, they are alsosubject to the adverse consequences of bloodtransfusion, including infection, pulmonary edema,immune suppression, and microcirculatory alter-ations.67 Traditionally, blood transfusions havebeen administered when the patient’s hemoglobinlevel is less than 10 g/dL or the hematocrit is lessthan 30%. However, a multicenter, prospective,randomized study of transfusion in ICU patients,the TRICC study (Transfusion Requirements inCritical Care), challenged this standard.68 A totalof 838 patients were randomized to receive bloodtransfusion based on a liberal (maintain hemo-globin level at 10–12 g/dL) versus a restrictive(maintain hemoglobin level at 7–8 g/dL) strategy.The restrictive strategy was at least as effectiveas the liberal strategy in critically ill patients. Signif-icant differences favoring the restrictive strategyincluded the in-hospital mortality rate, the cardiaccomplication rate, and organ dysfunction. Thisstudy suggested that blood transfusion shouldbe restricted to patients who have a hemoglobinlevel of less than 7 g/dL.

The impact of the TRICC study on transfusionpractices in the United States has been limited.The CRIT study, a prospective, multicenter, obser-vational study of ICU patients, analyzed the trans-fusion practices of 284 ICUs in 213 hospitals in the

United States.69 The mean pretransfusion hemo-globin level was 8.6 � 1.7 g/dL, indicating thatthe majority of patients were still being transfusedat a hemoglobin level higher than what was recom-mended in the TRICC study. Once again, thenumber of units of red blood cell transfusions thepatients received was independently associatedwith longer ICU length of stay and increasedmortality. The CRIT study excluded burn patients;thus, it provides no data on burn center transfusionpractices and the outcomes related to thosepractices.

Limited data exists regarding the effects ofa restrictive blood transfusion policy in adult burnpatients. In one study by Sittig and Deitch,70 14patients admitted to a burn center during a 6-month interval were transfused when their hemo-globin level was less than 6.0 g/dL. The outcomesof patients who had burns over less than 20% oftheir total body surface area or patients whorequired excision and grafting of less than 10%of their total body surface area were retrospec-tively compared with a matched group of 38patients who had been treated the previous yearusing a nonrestrictive policy (hemoglobin levelmaintained at greater than 9.5–10 g/dL). No differ-ences existed in the hospital length of stay. Thepatients treated using the liberal strategy received3.5 times as much blood as their restrictive-policycounterparts. Although this study is an importantfirst step in the evaluation of blood transfusion inburn patients, it is limited by its retrospectivenature, review bias, and inadequate number ofpatients.

To evaluate actual burn center transfusion prac-tices, the Burn Multicenter Trials Group reviewedthe actual use of blood transfusion in patientswho had burn injury to 20% or more of their totalbody surface area for a 1-year period.71 Datawas collected from 21 different burn centers ona total of 666 patients. The overall hemoglobinlevel at which the first transfusion was adminis-tered was 9.35 � 0.8 g/dL for all patients, andthe mean number of blood transfusions was 13.7� 1.1 units, with the vast majority of transfusionsgiven in the burn ICU (9.4 � 1.1). Mortality, as inother studies of transfusion, was related to thenumber of units of blood transfused. In addition,each transfusion increased the risk for infectionby 11%.

Three other retrospective studies were con-ducted to evaluate blood transfusion after burninjury: two in children and one in adults. One studyby Jeschke and colleagues72 that evaluated theuse of blood transfusion in 227 children who hadmajor burn injury demonstrated increased ratesof sepsis and mortality in children who received

What’s New in Critical Care of the Burn Patient? 611

more than 20 units of blood as compared withsimilar children receiving less than 20 units. Theother two studies, one in children and one inadults, demonstrated decreased mortality inpatients treated using a restrictive transfusionstrategy.73,74 Although these studies suggest thata restrictive transfusion strategy is efficacious,a prospective, randomized trial is needed to definethe optimal burn blood transfusion strategies. Inthe interim, the use of blood transfusion afterburn injury should be scrutinized.

SEPSIS PREVENTION ANDMANAGEMENT

Sepsis continues to be one of the leading causesof morbidity and mortality after burn injury. Recentadvances in sepsis treatment fall into several cate-gories: the development of sepsis guidelines, thedefinition of sepsis in burns, and the preventionof sepsis. This section provides an overview ofeach of these areas.

The development of sepsis guidelines was de-signed to standardize the treatment of sepsisthroughout all ICUs. The latest guidelines weredeveloped by an international panel of sepsisexperts spanning all ICU specialties.75 The guide-lines were created and rated based on availableevidence from the literature. The current recom-mendations for the treatment of sepsis, whichare broad based, include those listed in Box 1.

The applicability of these recommendations incertain aspects of burn treatment may be prob-lematic because the majority of the supportingdata does not include burn patients.

One of the major limitations in sepsis researchand the application of sepsis guidelines in patientswho have burns is a lack of a burn-specific defini-tion of sepsis. Although sepsis definitions havebeen developed for critically ill patients, their appli-cability in patients who have burns is limitedbecause of the innate differences in the physiologyof burn patients. For example, a burn patient ispersistently hypermetabolic, resulting in tachy-cardia, tachypnea, and elevated body tempera-ture. These physiologic alterations would result ina sepsis definition in the vast majority of patientswho have burn injury, many of whom would nothave an ongoing infection. To address theseissues, a consensus conference consisting ofburn experts from throughout the United Statesand Canada was held in January 2007 to definesepsis and infection for patients after burn injury.76

The findings of this group formed the foundationfor the diagnosis of sepsis in burns clinically andfor all future trials related to clinical burn sepsisand infection.

The definition of sepsis in the patient who hasburns requires that an infection be documentedby way of a positive culture result, a pathologictissue source, or a clinical response to antimicro-bials and three of the following:

1. Temperature greater than 39�C or less than36.5�C

2. Progressive tachycardia (adults, >110 beatsper minute; children, more than 2 SD aboveage-specific norms)

3. Progressive tachypnea (adults >25 beats perminute not ventilated, or with minute ventilation,>12 l/min ventilated; children, more than 2 SDabove age-specific norms)

4. Thrombocytopenia beginning 3 days after initialresuscitation (adults <100,000/ml; children, <2SD under age-specific norms)

5. Hyperglycemia in the absence of preexistingdiabetes mellitus (untreated plasma glucose>200 mg/dL, or equivalent mM/L or insulinresistance)

6. Inability to continue enteral feedings for morethan 24 hours.

These criteria form the foundation for all futureclinical studies and trials of sepsis in patientswho have burns.

Glycemic Control

Critically ill adults and children frequently developstress-induced hyperglycemia secondary to alter-ations in the control mechanisms for glucosesupply and demand.77 An ‘‘insulin-resistant’’ statedevelops, in which patients have either normal orelevated plasma insulin concentrations duringhyperglycemia.78 Early hyperglycemia andglucose variability after admission to the ICUhave been associated with adverse outcomes;prolonged hyperglycemia has been associatedwith a sixfold increase in mortality.79 Hypergly-cemia has also been associated with increasedmortality in severely burned children and adults,and the administration of exogenous insulin tominimize hyperglycemia after critical illness hasbeen shown to impact outcome in adult patients.80

In a landmark study, van den Berghe andcolleagues81 demonstrated that, in critically illpatients, intensive intravenous insulin therapy, de-signed to maintain normoglycemia (80–110 mg/dLplasma glucose level) reduced in-hospitalmortality by 34%. Similarly, patients who had dia-betes and acute myocardial infarction showedimproved long-term survival when they weretreated using insulin therapy that targeted a plasmaglucose level of less than 215 mg/dL.82

Box1Current recommendations for the treatmentof sepsis

1. Provide early, goal-directed resuscitationwithin 6 hours of sepsis diagnosis.

2. Check blood cultures before starting antibi-otic therapy.

3. Use imaging studies to confirm the infectionsource.

4. Start the administration of broad-spectrumantibiotics within 1 hour of diagnosis ofseptic shock or severe sepsis.

5. The narrowing of antibiotic coverageshould be based on culture sensitivityresults.

6. Use a 7- to 10-day antibiotic duration,guided by clinical response.

7. Use source control.8. Provide resuscitation using colloid or crystal-

loid agents.9. Use a fluid challenge to restore mean circu-

lating filling pressures.10. Use a reduction in fluid administration in

cases with rising filling pressures and noimprovement in tissue perfusion.

11. The vasopressor preference should be fornorepinephrine or dopamine to maintainthe target arterial pressure at greater than65 mm Hg when fluid resuscitation fails toimprove hemodynamics.

12. Use dobutamine when the cardiac outputremains low despite the use of fluid resusci-tation and combined inotropic and vaso-pressor therapy.

13. Use stress-dose steroid therapy only in casesof septic shock when the blood pressure ispoorly responsive to fluid and vasopressortherapy.

14. Provide recombinant-activated protein Cto patients who have severe sepsis anda high risk for death based on clinicalassessment.

15. Maintain hemoglobin levels at 7 to 9 g/dL,except in patients who have coronary arterydisease or acute hemorrhage.

16. Use low-tidal-volume ventilation and a limi-tation of inspiratory plateau pressure inpatients who have ALI and ARDS.

17. Minimize the positive end-expiratory pres-sure in patients who have ALI.

18. Use a conservative fluid managementstrategy for patients who have ALI andARDS who are not in shock.

19. Follow the protocols for weaning and seda-tion and analgesia.

20. Use intermittent bolus sedation or contin-uous infusion sedation with dailyinterruption.

21. Avoidance the use of a neuromuscularblockade.

22. Institute glycemic control that targetspatients who have a blood glucose level ofless than 150 mg/dL.

23. Maintain an equivalency of continuousveno-veno hemofiltration and intermittenthemodialysis.

24. Use prophylaxis for patients who havedeep-vein thrombosis.

25. Use stress ulcer prophylaxis with H2 blockersor proton pump inhibitors.

26. Consider the limitation of support, whenappropriate.

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Several studies have been completed evaluatingthe impact of tight glycemic control after major burninjury. Two studies, one in adults and one in chil-dren, have been performed in patients who hadburn injury.83,84 Both studies demonstrated thata strict glycemic control protocol that maintainedblood glucose levels at less than 120 mg/dL couldbe developed and safely applied for patients whohad burns, with an incidence of hypoglycemia of5%. These studies also demonstrated a decreasein infectious complications and mortality. Althoughthese studies are suggestive of a salutary effect ofcontinuous exogenous insulin administration,further prospective, randomized trials are neededto confirm these findings because other studiesof glycemic control in critical illness have reporteddiffering results.85–87 Perhaps some of thedisparity in findings can be explained by the vaga-ries of glucose measurement for strict glycemiccontrol protocols. Blood glucose levels candiffer by as much as 20%, based on whetherthe blood is drawn from a central venous cath-eter or an arterial line.88 In addition, anemiamay introduce an error rate of 15% to 20% inpoint of care glucose testing readings.89 Hence,care needs to be taken in the development ofa protocol, including planning how and whenblood glucose levels will be measured. Addi-tional care needs to be taken to avoid the devel-opment of hypoglycemia during dressingchanges, during operative interventions, andafter the administration of certain medications.

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