American Burn Association Clinical Practice Guidelines On Burn Shock Resuscitation

ABA GUIDELINES
American Burn Association Clinical Practice Guidelines on

Burn Shock Resuscitation
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Robert Cartotto, MD, FRCS(C)*,1, Laura S. Johnson MD, FACS, FCCP, FCCM2, ,
Alisa Savetamal MD FACS3, , David Greenhalgh MD, FACS4, , John C Kubasiak MD5, ,
Tam N. Pham MD6, , Julie A. Rizzo MD7,8, Soman Sen MD9, Emilia Main MI10,
This Clinical Practice Guideline (CPG) addresses the topic of acute fluid resuscitation during the first 48 hours
following a burn injury for adults with burns ≥20% of the total body surface area (%TBSA). The listed authors
formed an investigation panel and developed clinically relevant PICO (Population, Intervention, Comparator,
Outcome) questions. A systematic literature search returned 5978 titles related to this topic and after 3 levels
of screening, 24 studies met criteria to address the PICO questions and were critically reviewed. We recommend
that clinicians consider the use of human albumin solution, especially in patients with larger burns, to lower
resuscitation volumes and improve urine output. We recommend initiating resuscitation based on providing 2 mL/
kg/% TBSA burn in order to reduce resuscitation fluid volumes. We recommend selective monitoring of intra-
abdominal and intraocular pressure during burn shock resuscitation. We make a weak recommendation for clinicians
to consider the use of computer decision support software to guide fluid titration and lower resuscitation fluid
volumes. We do not recommend the use of transpulmonary thermodilution-derived variables to guide burn shock
resuscitation. We are unable to make any recommendations on the use of high-dose vitamin C (ascorbic acid),
fresh frozen plasma (FFP), early continuous renal replacement therapy, or vasopressors as adjuncts during acute
burn shock resuscitation. Mortality is an important outcome in burn shock resuscitation, but it was not formally
included as a PICO outcome because the available scientific literature is missing studies of sufficient population
size and quality to allow us to confidently make recommendations related to the outcome of survival at this time.
Key words: burns; shock; fluid resuscitation.
AMERICAN BURN ASSOCIATION CLINICAL burn shock resuscitation, and construction of this CPG was
PRACTICE GUIDELINES conducted between March 2022 and March 2023.
In 2020, the American Burn Association (ABA) began a

process to create new Clinical Practice Guidelines (CPGs). PURPOSE
The ad hoc CPG committee developed a standardized, evi-
dence-based process for CPG production, which is now in use The recommendations in this guideline are intended only to
by several Investigator Panels. An overarching goal will be to guide clinicians faced with any of the clinical questions we
harmonize the new CPGs with the ABA Quality Registry and have addressed. These recommendations do not rigidly define
burn center verification standards. The authors of this guide- the standard of care or best practice, they are not prescrip-
line represent the Investigator Panel for the topic of acute tive, and they do not replace bedside clinical judgement and
decision making by a clinician resuscitating a patient with an
acute burn injury. The recommendations are based upon a
systematic review of available literature with critical evalua-
1
Department of Surgery, Ross Tilley Burn Centre, Sunnybrook Heath Sciences
Centre, University of Toronto, Canada 2Department of Surgery, Walter L.
tion of only the studies meeting our clinical question criteria.
Ingram Burn Center, Grady Memorial Hospital, Emory University, Atlanta, Recommendations were based on the quality of and our con-
GA, USA3Department of Surgery, Connecticut Burn Center, Bridgeport fidence in the published evidence, and finally consideration of
Hospital, Bridgeport, CT, USA4Shriners Hospital for Children, Northern
California, Sacramento, CA, USA5Department of Surgery, Loyola University the values and preferences of clinicians and patients.
Medical Center, Maywood, IL, USA6Department of Surgery, University of For this CPG, the term “acute fluid resuscitation” refers
Washington Regional Burn Center, Harborview Medical Center, Seattle, to the provision of intravenous fluid during the first 48 hours
WA, USA7Department of Trauma, Brooke Army Medical Center, Fort Sam
Houston, San Antonio, TX, USA 8Uniformed Services University of Health following an acute burn injury in an adult involving at least
Sciences, Bethesda, MD, USA9Department of Surgery, Division of Burn 20% of the total body surface area (%TBSA). We recognize
Surgery, University of California, Davis, CA, USA 10Sunnybrook Health
Sciences Centre, Toronto, Canada.
that the definition of completion of acute fluid resuscitation is
*
Address correspondence to R.C. (email: [email protected]) nebulous and that resuscitation may continue between 48 and
72 hours post burn in some cases. However, we defined the
© The Author(s) 2023. Published by Oxford University Press on behalf of the
American Burn Association. All rights reserved. For permissions, please e-mail: first 48 hours post injury as the resuscitation period, because
[email protected]. almost all studies on acute fluid resuscitation examine only
https://doi.org/10.1093/jbcr/irad125 in this period. The term “burn shock” refers to inadequate
1
Journal of Burn Care & Research
2 Journal of Burn Care & Research, 2023, XX XXXX/XXXX 2023
perfusion of organs and tissues which follows an acute burn Striking the right balance between adequate resuscita-
≥20% TBSA. This CPG does not apply to the resuscitation of tion and over-resuscitation may be influenced by how fluids
other forms of shock that may occur after a burn injury, such are titrated. Both historically and currently, urinary output
as septic shock. (UOP) has been the primary guide to the titration of resus-
citation fluids. However, alternative approaches to titration
based on the use of malperfusion markers (lactate and base
USERS deficit), or hemodynamic endpoints (central venous pressure,
transpulmonary thermodilution-derived variables, or arte-
This CPG will be of most use to clinicians who provide acute
rial waveform analysis)13 or algorithm-based and computer
care to patients with major burn injuries (ie, burns ≥20%

supported decisions have been considered.14,15 A key question
TBSA). Most of the interventions or diagnostic procedures
is whether any of these approaches help to limit resuscitation
that we will consider in this CPG are carried out in the burn
volumes or improve fluid resuscitation outcomes, compared
center. Therefore, the recommendations primarily will guide
to using UOP alone.
burn care personnel who work in burn centers. However,
The content of the resuscitation fluid is of paramount im-
some material in this CPG will be of value to clinicians who in-
portance to the goal of adequately resuscitating the burn
itiate acute burn resuscitation in the Emergency Department.
patient with the least amount of fluid. Virtually, all resusci-
tation formulae specify that colloids should be introduced
CLINICAL PROBLEM AND SCIENTIFIC at some point during resuscitation.16 Human albumin and
BACKGROUND plasma are the major colloids of interest, and the question
of when to optimally introduce a colloid remains unresolved.
Readers of this guideline are encouraged to consult more With respect to albumin, various heterogeneous randomized
detailed reviews of the pathophysiology of burn shock and controlled trials (RCTs)17–20 and a meta-analysis21 of 3 of the
clinical burn resuscitation.1–3 This section is intended only RCTs17–19 suggest that early addition of albumin reduces total
to describe the relevant scientific background that informed resuscitation volumes. However, the effect of albumin use
our panel’s selection of important clinical questions related to on patient outcomes is entirely uncertain. Two study level
burn shock resuscitation. meta-analyses of the 4 RCTs17–20 found no effect of albumin
Following an acute burn to more than 20% of the BSA, on mortality.21,22 A different study level meta-analysis found
intravascular volume depletion, depressed cardiac output, and a trend toward increased mortality with the addition of al-
elevated systemic vascular resistance combine to compromise bumin.23 One meta-analysis,22 while recognizing substantial
perfusion to organs and tissues. Although it has long been study heterogeneity and that other outcomes were not uni-
recognized that fluid resuscitation is necessary to reverse this formly measured across all the RCTs, also found no effect of
process, the optimal methods of providing and monitoring albumin on compartment syndrome development, renal func-
fluid resuscitation remain uncertain. Insufficient resuscitation tion, or respiratory complications. The resurgence of interest
clearly will lead to organ failure and even death.4,5 However, in the use of human plasma during burn shock resuscitation
recognition of the phenomenon of “fluid creep”6 over 2 has largely been driven by the emerging understanding of the
decades ago has focused attention on the opposite problem: role of endotheliopathy in burn shock and the experimental
provision of excessive resuscitation fluid leads to increased observation of plasma’s restorative effect on the endothelial
morbidity and mortality in major burn patients.7,8 Thus, while glycocalyx post burn injury.24 Furthermore, modern forms
fluid resuscitation is necessary and life-saving, the intervention of plasma such as pathogen-reduced plasma and lyophilized
itself can cause harm. This paradox has generated numerous plasma have created new inroads into the use of plasma as a
practical clinical problems and questions for clinicians about volume expander during acute burn resuscitation.25,26 A va-
how to monitor and resuscitate acute burn patients. riety of retrospective studies and one small RCT have which
Central to this conundrum are the simultaneous problems have investigated plasma resuscitation have found that the use
of intravascular volume depletion and formation of soft of plasma reduced resuscitation volumes and edema.27–31 As
tissue and organ edema, which results predominantly from was the case with albumin, very little is known about plasma’s
an increase in microvascular permeability not only in the effects on other outcomes. An alternative to using colloids to
burn wound but also in unburned tissues and organs.9 resuscitate while limiting fluids is to add high dose vitamin
Re-expansion of the contracted plasma volume with intrave- C (ascorbic acid) to the resuscitation fluid. Preclinical studies
nous fluids necessarily worsens edema formation. Therefore, found that high doses of ascorbic acid, likely acting through
critical components of resuscitation that have been considered its antioxidant and free-radical scavenging properties, dramat-
to obtain balance between under and over-provision of fluid ically reduced crystalloid resuscitation volumes and edema
include the choice of resuscitation formula, how clinicians formation following experimental burns.32–35 In humans, the
respond and titrate fluids, the composition of resuscitation infusion 66 mg/kg/hour of ascorbic acid has been examined
fluids and the use of agents to limit microvascular leak and in a small number of studies, with mixed findings with respect
loss of intravascular fluids. to the outcome of reduction in resuscitation fluid volumes.36–39
While all burn resuscitation formulae are meant to guide Even less is known about other outcomes following the use of
only the initial rate of fluid infusion, the choice of formula high-dose ascorbic acid, and some concerns have been raised
may be important. Some studies suggest that use of the about a possible association with oxalate nephropathy and de-
Modified Brooke formula or alternative approaches may ad- velopment of AKI.37,40,41
equately resuscitate patients while limiting resuscitation Resuscitation failure may take various forms.42 Chiefly, it is
volumes compared to the widely-used Parkland Formula.10–12 characterized by diminishing urinary output and worsening
Volume XX, Number XX Journal of Burn Care & Research, 2023, XX 3
hemodynamic instability despite provision of escalating volume at 24 or 48 hours post burn, (b) increase urine output,
volumes of resuscitation fluids, and with the onset of dan- or (c) decrease edema-related complications?
gerous edema-related complications including pulmonary Question 5: For adult patients with a ≥ 20% TBSA burn
edema and compartmental syndromes of the abdomen, limbs, injury, does administration of high dose (66 mg/kg/hour)
and orbit. Resuscitation de-escalation and rescue approaches, ascorbic acid (vitamin C), compared to not using high dose
including the use of vasopressors,43 early renal replacement ascorbic acid, while providing crystalloids alone during acute
therapy (by translating the high-dose hemofiltration approach fluid resuscitation (a) reduce total crystalloid resuscitation
employed in septic shock with AKI),44 therapeutic plasma volume at 24 or 48 hours post burn, (b) increase urine output,
exchange45 and even extra-corporeal support46 are under- or (c) decrease edema-related complications?

studied topics where many clinical questions remain. Question 6: Among adults with burns ≥20% TBSA, during
acute fluid resuscitation should (a) CVP, (b) transpulmonary
thermodilution (TPTD), or (c) stroke volume variation(SVV)
METHODS or pulse pressure variation (PPV) from arterial waveform
The Investigator Panel for this CPG met virtually and analysis be used to titrate resuscitation fluids, compared to
communicated electronically between March 2022 and using hourly urine output either alone or in conjunction with
March 2023. Through a consensus discussion, and based “conventional” endpoints such as heart rate, blood pressure,
on the preceding scientific background, clinically relevant serum lactate, and arterial base deficit, to (a) reduce total fluid
questions pertaining to the topic of acute burn shock re- resuscitation volume or total crystalloid resuscitation volume
suscitation were developed. All questions were then placed at 24 or 48 hours post burn or (b) decrease edema-related
into a PICO format. Population: The patient population to complications?
which the question applies, Intervention: The therapeutic Question 7: Among adults with burns ≥20% TBSA, should
intervention(s) or diagnostic test of interest, Comparator: computerized decision support software (CDSS) compared to
The alternative approach being compared to the intervention using hourly urine output alone be used to titrate acute resus-
of interest, and Outcome: The outcome(s) of interest related citation fluids to (a) reduce total fluid resuscitation volume or
to the intervention(s) being examined. The Panel considered total crystalloid resuscitation volume at 24 or 48 hours post
outcomes that would be important to both clinicians and burn and (b) decrease edema-related complications?
patients. Many outcomes were considered, including sur- Question 8: Among adult patients with ≥20% TBSA burn
vival. Based on the aforementioned scientific background, injury undergoing acute fluid resuscitation who require a
the panel concluded that while mortality is important in vasopressor for hypotension, should norepinephrine or vas-
evaluating the success of any fluid resuscitation strategy, the opressin be the first administered vasopressor to (a) reduce
available studies are relatively small, heterogenous, and most 28-day mortality and (b) reduce acute kidney injury?
were not randomized controlled trial, thus diminishing our Question 9: Among adults with burns ≥20% TBSA, during
assurance about including mortality as a formal PICO out- acute fluid resuscitation, should early continuous renal re-
come. We anticipate that in future iterations of this guideline, placement therapy (CRRT) without fluid removal be initiated,
that mortality will be included as an outcome, as larger on- compared to not initiating CRRT to (a) reduce total fluid re-
going RCTs are completed. The following 10 questions were suscitation volume or total crystalloid resuscitation volume at
created by the panel: 24 and 48 hours post burn and (b) decrease edema-related
Question 1: Among adults with burns ≥20% TBSA, does complications?
the administration of albumin during the first 24 hours of Question 10: Among adults with burns ≥20% TBSA, should
fluid resuscitation, compared to using crystalloid fluid alone, (a) intra-abdominal pressure(IAP), (b) intra-ocular pressure
(a) reduce total fluid resuscitation volume or total crystalloid (IOP), (c) serum lactate (L), or (d) arterial base deficit be
resuscitation volume at 24 or 48 hours post burn, (b) increase monitored during the first 48 hours post burn compared to
urine output, or (c) decrease edema-related complications? not monitoring IAP, IOP, L, and BD, to (a) reduce total fluid
Question 2: Among adults with burns ≥20% TBSA should resuscitation volume or total crystalloid resuscitation volume
albumin be initiated early (<12 hours post burn) or late (after at 24 or 48 hours post burn or (b) reduce the incidence of ab-
12 hours post burn) during acute fluid resuscitation to (a) dominal compartment syndrome, or (c) orbital compartment
reduce total fluid resuscitation volume or total crystalloid re- syndrome?
suscitation volume at 24 or 48 hours post burn, (b) increase The outcome of “edema-related complications” was de-
urine output, or (c) decrease edema-related complications? fined as follows: any of the following occurring within the
Question 3: Among adults with burns ≥20% TBSA, does first 48 hours post burn: abdominal compartment syndrome
starting acute fluid resuscitation with 2 mL/kg/%TBSA burn (ACS), elevated intra-abdominal pressure (IAP), limb (ex-
compared to starting with 4 mL/kg/%TBSA burn (a) reduce tremity) compartment syndrome, orbital compartment syn-
total fluid resuscitation volume or total crystalloid resuscita- drome (OCS), elevated IOP, or pulmonary edema (radiologic
tion volume at 24 or 48 hours post burn, (b) affect the de- or reduced PaO2/FiO2 ratio in first 48 hours).
velopment of acute kidney injury, or (c) reduce edema-related
complications? SEARCH STRATEGY AND FINAL ARTICLE
Question 4: Among adults with burns ≥20% TBSA, should SELECTION
fresh frozen plasma (FFP) be used during acute fluid resusci-
tation compared to using crystalloids alone to (a) reduce total A systematic literature search strategy to address each question
fluid resuscitation volume or total crystalloid resuscitation was developed by a professional medical librarian (E.M.). To
address the relevant interventions, 7 concepts were identified: English language. Results were de-duplicated by an informa-
acute fluid resuscitation, crystalloids, vitamin C, CRRT, tion specialist (E.M.) using EndNote X9 (Clarivate Analytics
variables (eg, central venous pressure, stroke volume, etc.), LCC) and the methods outlined by Bramer et al.48 Searches
Computerized Decision Support Software, and vasopressors. were run from inception of the databases until May 17, 2022.
Concepts for albumin, fresh frozen plasma, and colloids were The search returned 9326 titles; 3342 were duplicates and
considered; however, testing with a sample set of articles in- were removed using the Bramer Method,48 leaving 5984
dicated significant overlap with the Acute Fluid Resuscitation titles which were uploaded and stored using Covidence
concept. In addition, 200 unique results from these concepts (Melbourne, Australia) reference management software, that
were screened by the lead author (R.C.) and determined to removed 6 further duplicates. The remaining 5978 titles and

be highly irrelevant; therefore, these concepts were not ex- abstracts were independently screened and reviewed by 2
plicitly included in the search. Each included concept was panel members (R.C. and L.J.). The 2 reviewers then met vir-
combined with a Burns concept using the Boolean AND, then tually and agreed that 5471 articles were irrelevant, and these
combined with the Boolean OR. The search was drafted in were dropped. The screeners then re-reviewed the remaining
Ovid Medline, then translated to additional databases using 237 articles on which they had originally disagreed and by
appropriate subject headings and syntax. The final searches consensus eliminated a further 167 titles, leaving 70 articles
utilized the following databases: Ovid Medline, Ovid Embase, selected for full text review (Figure 1). Three panel members
Ovid EBM Reviews: Cochrane Central Register of Controlled (R.C., L.J., and A.S.) then read these articles independently
Trials, Ovid EBM Reviews: Cochrane Database of Systematic and assessed whether the article should be critically reviewed
Reviews, and the Cumulative Index of Nursing and Allied and included in this CPG. To be included, 4 criteria needed
Health Literature (CINAHL) via EBSCO. In each database to be met: (1) the study needed to involve adults with burns
except the Cochrane Database of Systematic Reviews, animal ≥20% TBSA who received acute fluid resuscitation, (2) there
studies were excluded using a filter developed by the McGill had to be a defined intervention or investigation as specified
University Health Centre,47 and results were restricted to in our PICO questions, (3) there had to be a corresponding
Figure 1. PRISMA flow to show how initial list of titles was reduced to the 24 articles selected for final critical review and inclusion.
comparator as defined in the PICO question, and (4) at least suggesting that even in rescue situations, albumin appears to
one of our defined PICO outcome measures had to be re- have a fluid-sparing effect. One moderate-strength rescue
ported. The three panel members then met on December study found that despite having bigger and deeper burns, re-
12, 2022 and compared their individual observations and suscitation volumes in albumin-treated patients were similar
reached consensus on which studies to include. Unresolvable to those treated with crystalloid alone, inferring a volume-
disagreements were settled by a vote. This process identified sparing effect.50
24 studies for inclusion (Table 1).10,17,19,20,29,31,36–38,49–63 With respect to the outcome of UOP, one high strength
Finally, the 24 articles were critically reviewed and scored study showed a tendency to higher UOP in the albumin
independently by 3 panel members (R.C., L.J., A.S.) using treated patients.19 Most studies did not directly examine or

the method of Law et al.64 These reviewers then met virtu- report this variable. However, one might infer that the rapid
ally on December 12, 2022, compared reviews, and reached decline in the I:O ratio noted in 3 studies upon administering
consensus on the final score for each study (Table 2). We albumin50,52,53 might be indicative of not only a fluid-sparing
considered strength of evidence as high for a score of 12-14, effect but also promotion of diuresis.
moderate for a score of 9-11, and low for a score less than 9. The outcome of edema-related complications was the most
The rationale for each of the final scoring decisions is included difficult to assess because most studies did not report these
in Appendix 1. Authors were then assigned questions to draft or used unreliable or unreproducible or surrogate measures
a response and initial recommendation and then the panel of edema. We believe that in the absence of reporting com-
met virtually on March 8, 2023 to finalize recommendations partment pressures or strict criteria and definitions for diag-
through a consensus discussion. nosis of compartment syndrome, which outcomes such as
Question 1: Among adults with burns ≥20% TBSA, does the performing a fasciotomy or abdominal decompression are
administration of albumin during the first 24 hours of fluid re- operator-dependent, introduce a potential bias and are not
suscitation, compared to using crystalloid fluid alone, (a) reduce reliable. One high-strength study where albumin was used
total fluid resuscitation volume or total crystalloid resuscitation in a predetermined fashion, and not for rescue, found that
volume at 24 or 48 hours post burn, (b) increase urine output, or pulmonary edema significantly worsened over the first post
(c) decrease edema-related complications? burn week in albumin-treated patients, as assessed by meas-
We identified several studies17,19,20,50–54 which met our in- ured lung water (using gas rebreathing) and evaluation of
clusion criteria and that compared use of albumin to crys- chest radiographs.19 Considerations surrounding this finding
talloid alone during the first 24 hours of resuscitation, and are that it was assessed in only a subpopulation and not in
described at least one of our outcome measures (Table 1). all subjects, and the amount of free water and colloids given
These studies are extremely heterogeneous but can be after 24 hours, development of sepsis, and mechanical ven-
broadly classified based on how albumin was administered. tilation were not quantified and may have differed between
In one group of studies, albumin was started as a clinician- the colloid and crystalloid subjects. Interestingly, an earlier
directed response to rescue patients that were receiving large low-strength study by the same group51 demonstrated no dif-
amounts of crystalloids, and/or whose resuscitation was dete ference in lung water, and a high strength non-rescue study
riorating.49,50,52–54 In the other group of studies, albumin was saw no respiratory compromise in patients receiving colloids
administered as a predetermined resuscitation strategy.17,19,20,51 compared to patients receiving crystalloid alone.20 A study
The difference between these types of studies is important level meta-analysis found a lower odds of abdominal compart-
because in the rescue studies, patients administered albumin ment syndrome (OR 0.19, 95%CI, 0.07-0.5), with albumin
were generally sicker, had bigger and/or deeper burns, and infusion,22 but this analysis pooled data from heterogeneous
were already receiving large amounts of crystalloids. All of studies, including randomized, non-randomized, rescue, and
these factors can then potentially influence our outcomes of non-rescue studies.
interest. We did not look at mortality as an outcome, because we
With respect to the outcome of total crystalloid or resus- recognized that the available studies comparing crystalloid
citation volumes at 24 or 48 hours, we can only consider to colloid in burn shock resuscitation are underpowered and
the nonrescue studies, as these compared administration of too heterogeneous to confidently determine any relationship
albumin to crystalloid in patients who were similar at base- between colloid use and survival. Mortality is an important
line. Two high-strength studies showed either a significant outcome, and this decision should not minimize its rele-
decrease in resuscitation volume19 or a trend to lower resus- vance. Similarly, it should not be inferred that reduction in
citation volume20 with the use of albumin, compared to crys- resuscitation volume leads to lower or higher mortality. A
talloid alone. This effect was also observed in 2 low-strength useful analogy is seen with the use of the synthetic colloid
studies.17,51 Most of the rescue studies found that resusci- hydroxyethyl starch (HES), which may reduce fluid volumes
tation volumes in patients receiving albumin were actually but which has adverse effects on renal function and survival.65
higher than when crystalloid alone was given.49,52–54 However, In short, we need larger high-quality RCTs (eg, the ongoing
in all cases, albumin was administered by clinician direction ABRUPT 2 study, NCT04356859) to determine albumin’s
to patients with bigger and/or deeper burns or who were re- effect on the important outcome of survival.
ceiving very large amounts of crystalloid already. Although Mortality outcomes in our selected studies for this question
these rescue studies cannot directly answer the question re- are shown in Table 1. Two random effects meta-analyses21,22
garding the outcome of resuscitation volumes, a highly im- pooled study level data from 4 RCTs17–20 (one of which was
portant observation from three studies50,52,53 was that the not included in our final selection because the comparison in-
initiation of albumin rapidly lowered the in-to-out (I:O) ratio, cluded hypertonic lactated saline)18 and found no effect of
Table 1. Study details.
Total PICO-relevant Other relevant
Author Design N Sample outcomes outcomes Intervention and comparator Results
Q1: Albumin vs. crystalloid

Cochran Case control 202 ALB: N = 101, age 38 ± 21 Resuscitation SIRS/sepsis ALB: 5% infusion 1:2 with LR • Mean resuscitation volume at 53 ± 40
200749 (controls matched years, %TBSA burn 42 volume* ARDS within first 24 hours, at hours post burn was 9.4 ± 6.4 mL/
for age and ± 18, %FT burn 23 ± *a 24-hour volume mortality clinician’s discretion if re- kg/%TBSA burn in ALB vs. 6.4 ± 4.4
%TBSA burn) 16, INHI 51%* was not specified. suscitation volume exceeded mL/kg/%TBSA burn at 36 ± 24 hours
Control: N = 101, age 36 Volume was Parkland for ≥ 2 consecu- in control (P < .001)
± 21, %TBSA burn 40 ± “required for re- tive hours, titrated to UOP, • No difference in SIRS/sepsis or mortal-
16, % FT burn 14 ± 21, suscitation” until terminated when resuscita- ity, ALB 3 times more likely to develop
INHI 18% “maintenance tion at maintenance rate. ARDS during hospitalization, but only
*P < .001 vs. control rate achieved.” Control: LR titrated to UOP INHI independently associated with
ARDS. ALB associated with lower risk of
6 Journal of Burn Care & Research, 2023, XX
mortality.
Comish Case control 91 Colloid: N = 30, age 44 ± 24-hour crystalloid In to out ratio Colloid: 25% albumin (0.1 mL/ • 24 hours LR was 4.3 ± 1.8 mL/
202150 3 years, mean% TBSA resuscitation (IOR) kg/%TBSA burn) started kg/%TBSA burn in colloid vs. 3.6 ± 1.2
burn 40*, mean % FT fluid volume LOS in first 24 hours for oliguria in crystalloid (P = .129)
burn 16**, INHI 4% Compartment syn- ICU LOS or unstable vital signs at • Compartment syndrome 3% in colloid
crystalloid: N = 61, age 45 drome ARDS clinician’s discretion. Fluids vs. 0% in crystalloid (P = .33)
± 2 years, mean %TBSA Mortality titrated to UOP > 0.5 mL/ • IOR reduced by 50% within 1 hour of
burn 34, mean % FT kg/hour starting 25% albumin. No differences in
burn 1, INHI 10% Crystalloid: LR only in first 24 ARDS or mortality. LOS and ICU LOS
*P = .047, **P = .005 vs. hours, titrated to UOP > 0.5 significantly greater in colloid
crystalloid mL/kg/hour
Both groups received albumin
after 24 hours
Cooper Randomized 42 Treatment: N = 19 age 36 24-hour resuscita- MODS Treatment: 5% albumin • Basal and resuscitation fluid in treat-
200620 controlled trial (24-45) year, % TBSA tion fluids Mechanical Control: LR ment were 1308 (480-1980) mL + 3355
burn 39 (32-53), %FT PaO2/FiO2 ratio ventilation Fluids titrated in both groups (2588-9138) mL vs. 1500 (720-2450) +
burn 15(0-43), INHI (daily/14 days) 28-day mor- to UOP > 0.5 mL/kg/hour 6178 (3435-9481) in control (P = .42)
63% tality and MAP > 70 mmHg • No differences in PaO2: FiO2 except on
Control: N=23, me- days 1 and 7
dian Age 31 (25-39), • No significant differences in MODS,
%TBSA burn 32 (26- duration ventilation or 28-day survival
34), %FT burn 12
(0-20)
Goodwin CC 24 Individual group charac- Resuscitation Colloid: 2.5% albumin in LR • Colloid resuscitation volume 2.68 ± 1.18
198151 teristics not presented. volume Crystalloid: LR mL/kg/%TBSA burn vs. crystalloid
Overall cohort (N = Measured lung Fluids titrated to UOP 30-50 resuscitation volume 3.62 ± 1.24 mL/
24) mean age 27 (range water mL/hour in both groups kg/%TBSA burn (P < .01)
18-42) and mean % • No differences in lung water on PB days
TBSA burn 47% (range 0-7
28%-79%)
XXXX/XXXX 2023

Table 1. Continued

Goodwin RCT 79 Colloid: N = 40 age 28 ± 24-hour resuscita- Cardiac index Colloid: 2.5% albumin in LR • 24 hours fluids: colloid 2.98 ± 1.1 mL/
198319 7, %TBSA burn 53 ± tion fluids EDVI Crystalloid: LR kg/%TBSA burn vs. crystalloid: 3.81 ±
17, no INHI Radiographic pul- Fluids estimated at 2 mL/ 1.48 mL/kg/%TBSA burn (P < .01)
Crystalloid: N = 39, age 28 monary edema kg/%TBSA burn and titrated • Radiologic pulmonary edema first 7 days
Volume XX, Number XX
± 8 years, % TBSA burn Measured lung to UOP 30-50 mL/hour in 20% in colloid vs. 4% in crystalloid
48 ± 12, no INHI water both groups • (N = 50) Lung water by day 7 signifi-
cantly greater in colloid vs. crystalloid

• (N = 29) EDVI and CI significantly
higher between 12 and 24 hours in col-
loid vs. crystalloid.
Greenhalgh CC (observa- 379 Albumin N = 253, age 48 24-hour total fluid In to out ratio Albumin: 5%, 25% or both in • Total 24 hours fluids: albumin: 5.2 ± 2.3
202152 tional non- ± 16 y*, %TBSA burn 24-hour UOP (IOR) first 24 hours per center’s mL/kg/%TBSA vs. crystalloid: 3.7 ± 1.7
NB: This protocolized 36(19.5)* *, %FT burn Fasciotomy for Duration venti- resuscitation approach and mL/kg/%TBSA burn
study also multicenter 15(26)**, 17.4% INHI compartment lation clinician’s discretion • 24 hours UOP: albumin 0.8 ± 0.46
addressed study) Crystalloid: 43 ± 15 years, syndrome at 48 In-hospital sur- Crystalloid: LR only in first 24 mL/kg/hours vs. 0.96 ± 0.57 mL/kg/
Q2: early % TBSA burn 25 ± 11, hours vival hours per center’s resuscita- hours crystalloid
vs. late al- %FT burn 0 (8), 3.2% ACS at 48 hours RRT in first 96 tion approach and clinician’s • Fasciotomy 3.6% in albumin vs. 0% in
bumin. INHI hours discretion crystalloid.
*P < .003 vs. crystalloid • ACS in first 48 hours: 0.8% in albumin
**P < .001 vs crystal- vs. 0% in crystalloid
loid • Immediate drop in IOR upon starting
albumin
• RRT, duration vent, and mortality all
greater in albumin
Lawrence CC 52 Colloid (N = 26) age 42 ± Resuscitation In to out ratio Colloid: LR changed to 5% al- • Colloid: 6.9 ± 3.1 mL/kg/%TBSA burn
201053 3 years, %TBSA burn volume* (IOR) bumin in 1:2 ratio with LR at median 37 hours PB crystalloid 4 ±
40 (23-87) * % FT *a 24-hour volume Mortality in first 24 hours for high 2 mL/kg/%TBSA burn at median 30
burn 15 (0-76), 46% was not specified. volume requirements or hours PB (P < .001)
INHI Volume was edema complications • Immediate drop in IOR upon starting
Crystalloid (N = 26) 42 ± for resuscita- Crystalloid: LR only albumin
3 years, % TBSA burn tion until UOP Both groups titrated to UOP • No difference in mortality
28 (20-59), % FT burn maintained at a goal 30-50 mL/hours, and
(0-24), 27% INHI calculated main- completed when mainte-
*P = .005 vs. crystalloid tenance rate nance rate achieved.
Journal of Burn Care & Research, 2023, XX 7

Table 1. Continued
Park 201254 CC 159 Preprotocol: N = 98 age 43 24-hour resuscita- Ventilator days Preprotocol: LR at 4 mL/ • 24 hours fluids: preprotocol 4.6 ± 2.3
(historical control) ± 18, % TBSA burn 39 tion fluids Mortality kg/%TBSA burn, titration mL/kg/%TBSA burn vs 4.2 ± 1.7 mL/
± 18, 42% INHI ACS requiring lapa- not described + vasopressors kg/%TBSA burn postprotocol (NS)
Postprotocol N = 61 age rotomy at clinician’s discretion • ACS with laparotomy 6% preprotocol vs.
41 ± 19 years, %TBSA PaO2:FiO2 ratio at Postprotocol: LR but at 0% postprotocol (P < .05).
burn 38 ± 18, 40% 24 hours 12 hours, if 24-hour • PaO2:FiO2 ratio at 24 hours significantly
INHI projected fluids are ≥ 6 higher in postprotocol
mL/kg/%TBSA burn, LR • Significant reduction in ventilator days
changed to 5% albumin + and mortality in postprotocol
possible additional colloids,
eg, blood, hespan, FFP,
(colloids used in 41% post

protocol). Also vasopressin
infusion started, titrated to
BP, additional NE given for
hypotension, IAP measured
q 4 hours. Titration of fluid
if UOP ≥ 1 mL/kg/hour.
Recinos RCT (pseudoran 15 ADULT analysis (age 24-hour fluid LR+ ALB: 2.3% albumin in LR • 24 hours fluid volume: LR+ ALB: mean
197517 domized) 13-59) volume LR: LR only 2 (range 1.1-3.8) mL/kg/%TBSA burn
LR +ALB, N = 9, mean Edema No resuscitation formula used, vs. LR mean 2.9 (range) 1.7-4.9. (P =
%TBSA burn 57% complications fluids titrated in both groups .001)
LR: N = 6 mean % TBSA to 30-50 mL/hours. • No edema complications in LR +ALB
burn 54% vs. 3 cases with complications in LR.
Greater use of diuretics in LR than LR +
ALB
• No mortality difference
Q3: 2 mL/kg/%TBSA burn Vs. 4 mL/kg/%TBSA burn

Chung CC 52 Modified Brooke N = Total 24-hour fluids Ventilator-free Modified Brooke: Resuscitation • 24 hours total fluids: modified Brooke:
200910 31, age 25 ± 5 years, 24-hour UOP days initiated with LR based on 2 3.8 ± 1.2 mL/kg/%TBSA burn vs. 5.9 ±
%TBSA burn 55 ± 19, admission PaO2/ Mortality mL/kg/%TBSA burn 1.1 mL/kg/%TBSA burn (P < .001)
% FT burn 46 ± 22 4 % FiO2 ratio ACS Parkland: resuscitation initiated • 24 hours UOP modified Brooke 1638
INHI (laparotomy- with LR based on 4 mL/ ± 477 mL vs. Parkland 1818 ± 455 mL
Parkland: N = 21, age 25 defined) kg/%TBSA burn (NS)
± 5, %TBSA burn 46 ± Fluids titrated to 30-50 mL/ • No mortality difference
17, % FT burn 39 ± 20, hours UOP goal in both. • No differences in PaO2:FiO2, vent free
29% INHI Albumin allowed in both days, ACS, AKI, or mortality
if 24-hour fluid projection
at 12 hours PB exceeded 6
mL/kg/%TBSA burn
XXXX/XXXX 2023

Table 1. Continued

Saitoh RCT 36 Modified Brooke: N = 17, Resuscitation fluid 28-day and Modified Brooke: LR based on • Fluid volume at 24 hours: Modified
202155 age 59 ± 20, %TBSA volume at 24 hospital 2 mL/kg/%TBSA burn, Brooke: 3.6 ± 1.1 mL/kg/hours vs.
burn 39 (27-49), %FT hours survival fluid rate adjusted q 2 hours 4.59 ± 1.58 mL/kg/hour in Baxter (P =
burn 10 (1-31), INHI AKI in first 48 hours by one-third for goal UOP .05).
24% ACS 0.5 mL/kg/hour. • No differences in PaO2:FiO2 ratios, AKI
Baxter: N =19, age 64 ± PaO2:FiO2 ratios to Baxter: LR based on 4 mL/ in first 48 hours, ACS, or survival
22, %TBSA burn 30 day 7 kg/%TBSA burn, fluid

(25-51), %FT burn 18 rate adjusted q 2 hours at
(0-23.5), INHI 21% clinician’s discretion “based
on treatment policy of insti-
tution” for goal UOP 0.5
mL/kg/hours.
and/or FFP in first 24 hours
Q4: FFP vs. crystalloid
Du 199129 CC 30 LR: N = 10, age 39 ± 4 24-hour fluid Survival LR: initiated at 4 mL/ • 24-hour infusion volume: LR 4.8 ± 0.6
year, %TBSA burn 47 ± volume 24-hour kg/%TBSA burn adjusted mL/kg/% TBSA burn, HPT: 3.16 ± 0.4
4, % FT burn 23 ± 3 UOP Weight to UOP goal of 0.5 mL/ mL/kg/%TBSA burn, FFP: 2.7 ± 0.2
FFP, age 43 ± 4, % TBSA gain at 24 and kg/%TBSA burn mL/kg/%TBSA burn (P < .01).
burn 44 ± 4, % FT burn 48 hours FFP: basal LR at 84 mL/hour • 24-hour UOP LR: 0.9 ± 0.1 mL/kg/
22 ± 4 + FFP 75 mL/kg/36 hours, hour HPT: 0.97 ± 0.15 mL/kg/hour,
HPT(hypertonic crystal- adjusted to UOP goal of 0.5 FFP: 0.7 ± 0.1 mL/kg/hour (NS)
loid): Age 34 ± 5 year, mL/kg/hour • % Weight gain by 48 h: LR: 14%, HPT
%TBSA burn 50 ± 4, % HPT: hypertonic sodium ac- 12%, FFP 4% (P < .01)
FT burn 25 ± 7 etate initiated at 4 mL/
kg/%TBSA burn, adjusted to
UOP goal 0.5 mL/kg/hour
O’Mara RCT 31 Crystalloid N =15, age 46 24-hour fluid BD Crystalloid: LR at 4 mL/ • 24 hour fluid volume crystalloid 0.26 ±
200531 ± 21, %TBSA burn 50 ± volume PAP kg/%TBSA burn titrated to 0.12 L/kg (5 mL/kg/%TBSA burn) vs.
12, % FT burn 28 ± 12, 24-hour UOP Survival achieve UOP 0.5-1 mL/ 0.14 ± 0.1 L/kg (2.7 mL/kg/%TBSA
INHI 73% IAP kg/hour burn) in plasma (P = .005).
Plasma N = 16, age 45 ± weight gain Plasma: Basal LR at 83 mL/ • 24-hour UOP crystalloid: 0.77 ± 0.21 mL/
19, %TBSA burn 52 ± hour + FFP at 75 mL/ kg/hour vs. 0.76 ± 0.33 mL/kg/h (NS)
12, % FT burn 29 ± 19, kg/24 hour titrated to • Peak and change in IAP and % weight
INHI 63% achieve UOP 0.5-1 mL/ gain significantly greater in crystalloid
kg/hour than plasma
• Significantly greater correction of BD in
plasma than crystalloid
• PAP significantly higher in crystalloid
• No survival difference

Table 1. Continued

Q5: High dose ascorbic acid vs. no ascorbic acid

Flores CC (historical 75 HDAA: N =25, age 42 ± 24-hour resuscita- 72-hour fluids HDAA: LR + vitamin C at 66 • 24-hour fluid 3.1 ± 0.9 mL/kg/%TBSA
202256 control) 13 y, %TBSA burn 52 ± tion fluids ARDS mg/kg/hour for 36 hours burn in HDAA Vs. 4.3 ± 1.5 mL/
18*, INHI 24% 24-hour UOP AKI Control: LR only kg/%TBSA burn in control (P < .05)
Control: N = 50, age 47 ± Compartment syn- EVLWI Both groups resuscitated to • UOP 1.5 ± 0.7 mL/kg/hour in HDAA
16 year, %TBSA burn drome Mortality TPTD endpoints, both vs. 1.2 ± 0.4 mL/kg/hour in control (P
39 ± 16, INHI 32% groups given “colloids” > 12 = .13)
*P < .01 vs. control h if vasopressors required. • Compartment syndrome 20% in HDAA
vs. 24% in control (P = .7)
• No differences in 72-hour fluids,
EVLWI, ARDS, AKI, mortality
Kahn 201138 CC 33 Vitamin C: N = 17, 42 ± Resuscitation Renal failure Vitamin C: LR + 66 mg/kg/ • 24-hour fluids: 5.3 ± 1 mL/kg/%TBSA
16 yr %TBSA burn 45 ± volume in first Mortality hour Vitamin C continued burn in vitamin C vs. 7.1 ± 1 mL/
21, INHI 24% 24 hour to “approximately 24 h” kg/%TBSA burn in LR Only (P < .05).
LR only: 50 ± 20 year, Urine output in first LR only: LR • UOP in 24 hours: 1.5 ± 0.4 mL/kg/
%TBSA burn 39 ± 15, 24 hour. Com- Both groups titrated to UOP hour in vitamin C vs. 1 ± 0.5 mL/kg/
INHI 25% partment syn- > 0.5 mL/kg/hour and hour in LR Only (P < .05)
drome “stable hemodynamics.” • Fasciotomy 18% in vitamin C vs. 19% in
ACS LR Only. (NS)
PaO2:FiO2 ratio • ACS in 0 vitamin C vs. 6% in LR only
(NS)
• No differences in PaO2/FiO2 first 48
hours
• No differences in mortality
Lin 201837 CC (age and burn 80 HDAA: N =38, age 41 ± Total resuscitation ARF requiring HDAA: LR + Vitamin C at 66 • 24-hour fluids: HDAA 4.6 ± 2.6 mL/
size-matched 15, %TBSA burn 47 21, fluid at 24 hours dialysis mg/kg/h kg/%TBSA burn vs. 4.3 ± 2.5mL/
controls) ± 52%, INHI. Total 24-hour UOP Ventilator days Control: LR kg/%TBSA burn in Control(P = .6).
Control N = 42, age 42 ± Abdominal com- Mortality Both groups titrated “based on • Median 24-hour UOP HDAA 1.1(0.9-
17, %TBSA 43 ± 23, partment syn- Parkland formula.” 1.6) mL/kg/hour vs. 0.81 (0.6-1) mL/
36% INHI drome kg/hour in control P = .002
• ACS in HDAA 5.2% vs. 2.3% in control
• ARF/dialysis 23% in HDAA vs. 7% in
control (P = .06), vitamin C independ-
ently associated with ARF/dialysis (OR
5.4, 1.1-26), no differences in ventilator
days or mortality
XXXX/XXXX 2023

Table 1. Continued

Tanaka RCT (pseudo- 37 Ascorbic acid: N = 19, age Total resuscitation Duration venti- Ascorbic acid: 66 mg/kg/ • 24 hours fluids: 3 ± 1.7 mL/kg/%TBSA
200036 randomized) 40 ± 20 years, %TBSA volume at 24 lation hour for the first 24 hours burn in ascorbic acid vs. 5.5 ± 3.1 mL/
burn 63 ± 26, %FT hours Mortality postburn. kg/%TBSA burn in control (P < .004).
burn 51 ± 26, 79% UOP at 24 hours Control: LR alone • UOP in 24 hours: 1.3 ± 0.6 mL/kg/
INHI Compartment Fluids titrated to “stable hemo- hour in ascorbic acid vs. 1.1 ± 0.3 mL/
Control: N =18, age 49 ± syndrome dynamic measurements” and kg/hour in control (NS)
22, %TBSA burn 53 ± PaO2:FiO2 0-96 UOP 0.5-1 cc/kg/%TBSA • Fasciotomy 21% in ascorbic acid vs. 44%
17, % FT burn 40 ± 13, hours PB burn in both groups. Both in control (NS)
67% INHI groups received 5% albumin • PaO2:FiO2 ratios significantly higher in
after 24 hours. ascorbic acid from hours 18-96
• Ascorbic acid group had significantly less
soft tissue edema, acute weight gain, and
duration of ventilation
Q6: Semi-invasive monitoring vs. UOP and conventional parameters
Aboelatta CC 30 Group I (TPTD): N = Average daily resus- Mortality Group I (TPTD): LR initiated • Average 24 hours fluid volume (over first
201357 15, age 30 ± 15 year, citation fluid based on Parkland Formula, 72 hours): Group I (TPTD) 10 378 ±
%TBSA burn 41 ± 11 adjusted to achieve ITBVI 3723 mL vs. group II (control): 5917 ±
Group II (control): N = > 800 mL/m2, CI > 2.5 L/ 1695 mL (P < .001)
15, age 35 ± 11 years, min/m2, EVLWI > 10 mL/ • No survival difference
%TBSA burn 39 ± 9 kg above normal range,
additional vasopressors for
hypotension or oliguria,
4% gelatin boluses after 24
hours to 72 hours for hypo-
volemia
Group II (Control) LR initiated
based on modified Parkland
(3 mL/kg/%TBSA burn),
adjusted to MAP > 60, UOP
> 0.5 mL/kg/hour, lactate
< 2 mmol/L, ScvO2 > 65%.
Additional vasopressors for
hypotension or oliguria,
4% gelatin boluses after 24
hours to 72 hours for hypo-
volemia

Table 1. Continued

Chen CC 34 EGDT (early goal-directed Fluid volume Lactic acid EGDT: 1:1 crystalloid: colloid, • Fluid volume: EGDT: 3.29 ± 0.26 mL/
201758 therapy): N = 13, mean UOP Mortality dopamine, and dobutamine kg/%TBSA burn vs. CG: 3.71 ± 0.3
age 32 year, %TBSA PaO2/FiO2 ratio titrated to GEDVI 650- mL/kg/%TBSA burn (P < .05)
burn 89 ± 4 800 mL/m2, EVLWI 3-7 • UOP: EGDT: 0.83 ± 0.12 vs. CG: 0.85
CG (conventional group): mL/kg, SVI 40-60 mL/ ± 0.2 mL/kg/hour (NS)
N = 21, mean age 33 m2, SVRI 1200-1800 • PaO2/FiO2: EGDT: 381 ± 67 vs. CG:
year, % TBSA burn 86 d·s·cm−5·m2, MAP > 65 329 ± 49 (P < .05)
± 6. mmHg, UOP ≥ 1 mL/kg/ • Lactate: EGDT: 2 ± 0.6 mmol/L vs.
hour CG: 3.9 ± 1.2 mmol/L (P < .05).
CG: Conventional monitoring • Mortality EGDT 8% vs. CG 14%
and “traditional formula
(First Affiliated Hospital of

PLA General Hospital)”
Foldi 200959 RCT 16 ITBVI: N = 8, age 59 24 hours Lactic acid ITBVI: resuscitation fluids • 24 hours administered fluid: ITBVI:
(21-74), %TBSA burn administered CI at 24 hours titrated q 2 hours to achieve 5.5 (4.4-6.2) mL/kg/%TBSA burn vs.
37 (27-58), %FT burn fluid ITBVI 800-850 mL/m2 HUO: 4.3 ((4.2-5.2) (P < .05)
36(27-55), INHI 75%. 24 hours UOP HUO: resuscitation fluids • 24 hours UOP ITBVI: 1.1 (0.9-1.3
HUO (hourly urine titrated q 2 hours to achieve mL/kg/hour) vs. HUO 0.7 (0.5-1.1)
output) N = 8, age 54 UOP 0.5-1 mL/kg/%TBSA mL/kg/hour (P < .05)
(20-70) year, % TBSA burn. • CI at 24 hours: ITBVI: 3.5 (3.2--3.9)
burn 38 (29-61), % FT Resuscitation initiated with LR vs. HUO: 2.9 (2.3-3.5) (P < .05)
burn 35 (26-58), INHI at 4 mL/kg/%TBSA burn • No difference in lactate but more di-
88% in first 24 hours in both minished oxidative stress on days 3-6 in
groups, LR + hydroxyethyl ITBVI than HUO
starch administered after 24
hours in both groups.
Foldi 201060 RCT 30 ITBVI: N = 15, age 58 24 hours Lactic acid ITBVI: Resuscitation fluids • 24 hours administered fluid: ITBVI:
(22-75), %TBSA burn administered CI at 24 hours titrated q 2 hours to achieve 5.4 (4.2-6.6) mL/kg/%TBSA burn vs.
44 (33-62), %FT burn fluid Duration venti- ITBVI 800-850 mL/m2 HUO: 4.5 (4.1-5.4) (P < .05)
35(27-58), INHI 80%. 24 hours UOP lation HUO: resuscitation fluids • 24 hours UOP ITBVI: 1.1 (0.9-1.3
HUO (hourly urine ACS mortality titrated q 2 hours to achieve mL/kg/hour) vs. HUO 0.8 (0.6-1.1)
output) N = 15, age UOP 0.5-1 mL/kg/%TBSA mL/kg/h (P < .05)
56(23-65) year, % burn. • CI at 24 hours: ITBVI: 3.6 (3.3--3.9)
TBSA burn 42 (31-64), Resuscitation initiated with LR vs. HUO: 2.8 (2.4-3.2) (P < .05)
% FT burn 34 (28-56), at 4 mL/kg/%TBSA burn • No differences in lactate, ACS, duration
INHI 87% in first 24 hours in both ventilation, mortality.
groups, LR + hydroxyethyl
starch administered after 24
hours in both groups.
XXXX/XXXX 2023

Table 1. Continued

Holm RCT 50 TDD (transpulmonary 24-hour fluid Lactic acid TDD: LR initiated at 4 mL/ • 24-hour fluids: TDD: 27 064 mL vs.
200461 thermodilution) N = administered Cardiac index kg/%TBSA burn, adjusted to Baxter: 16 232 (P = .001)
25, mean age 37 years, 24-hour UOP Renal failure achieve ITBVI > 800 mL/ • UOP at 24 hours: TDD 205 ± 127 mL/
% TBSA burn 42%, Lung water requiring m2, CI > 3.5 L/min/m2, hours vs. Baxter: 123 ± 93 mL/hour (P
INHI 44% (EVLWI) dialysis and EVLWI < 10 mL/kg = .01)
Baxter: N = 25, mean age Mortality above normal • No differences in EVLWI to 48 hours.
45 years, % TBSA burn Baxter: LR initiated at 4 mL/ • CI significantly higher in TDD than
42%, INHI 56% kg/%TBSA burn, adjusted to Baxter only at 24 hours.
achieve UOP > 0.5 mL/kg/ • No differences in lactate, renal failure,
hour, and MAP >70 mmHg mortality
and CVP > 6 mmHg
± hydroxyethyl starch after
24 hours.
Zhu 202162 CC 191 Study group N = 82, age 24-hour resuscita- AKI Study group: Fluids adjusted • 24-hour resuscitation fluid vol-
41 ± 12 years, % TBSA tion fluid volume AEDS using “EDVI, ITBVI, CI, ume: Study group: 2.29 ± 0.4 mL/
burn 55 ± 12, % FT Survival SVRI, and EVLWI” (no kg/%TBSA burn vs. control group: 2.59
burn 15 ± 7, INHI 48% thresholds described) ± 0.39 mL/kg/%TBSA burn (P < .001).
Control group: N = 109, Control group: Fluids adjusted • AKI higher in control (29%) vs. 16% in
age 43 ± 12 years, % “according to HR, BP, study group (P = .03).
TBSA burn 53 ± 12, urine volume, resp rate, • No difference in ARDS, mortality
%FT burn 18 ± 7*, and SpO2” (no thresholds
INHI 39% described)
*P = .02 vs. study group Both groups resuscitated with
1.5 mL/kg/%TBSA burn
+2000 mL in first 24 hours
as 2:1 ratio of LR: Colloid
(FFP or 5% albumin).

albumin on mortality. This approach using pooled data from
trol 6.5 ± 4.1 mL/kg/%TBSA burn (P <

4.2 ± 1.8 mL/kg/%TBSA burn vs. con-
• 24-hour total resuscitation fluid: CDSS:
Index; LOS: lengthy of stay; LR: lactated ringers solution; MAP: mean arterial pressure; MODS: multiple organ dysfunction syndrome; NE: norepinephrine; PAP: peak airway pressure; PaO2/FiO2: ratio of arterial partial
Abbreviations: ACS: abdominal compartment syndrome; AKI: acute kidney injury; ALB: albumin; ARF: acute renal failure; ARDS: acute respiratory distress syndrome; BD: base deficit; BP: blood pressure; CC: case con-
pressure of oxygen to fractional inspired oxygen concentration; PB: post burn; RCT: randomized controlled trial; RRT: renal replacement therapy; SIRS: Systemic Inflammatory Response Syndrome; SVI: Stroke Volume
very heterogeneous studies has been criticized, and when an
trol; CDSS: Computer Decision Support Software; CI: Cardiac Index; EDVI: End-Diastolic Volume Index; EVLWI: Extra Vascular Lung Water Index; FFP: fresh frozen plasma; FT: full thickness; GEDVI: Global End-
• Vent-free days and mortality lower in
Diastolic Volume Index; HDAA: high-dose ascorbic acid; IAP: intra-abdominal pressure; ICU LOS: intensive care unit length of stay; IOR: in-to-out ratio; INHI: inhalation injury; ITBVI: Intrathoracic Blood Volume
• Hourly UOP in target range 31% in
alternative fixed-effects model with these RCTs was used, al-
CDSS vs. 23% in control (P < .05).

bumin was actually shown to be associated with higher mor-
tality.23 A recent Cochrane Systematic Review of colloid versus
crystalloid studies in critically ill patients (including burns) de-
Results
termined that it was unlikely that albumin or crystalloid use

made any difference to mortality.66
We recommend that clinicians consider providing albumin
CDSS (P < .05)

in the first 24 hours of resuscitation to improve urinary output
and to reduce the total volume of resuscitation fluids. The
strength of this recommendation is greater for patients with
.05)
larger burns, and weaker for patients with smaller burns.

We also recommend administration of albumin in “rescue”
situations where resuscitation is deteriorating despite re-
achieve target UOP 30-50 mL/
target UOP 30-50 mL/hour

Intervention and comparator
ceiving escalating amounts of crystalloids. We have low con-

LR to achieve a target UOP
from CDSS recommendation
hour; provider able to deviate
Both groups resuscitated with

Control: Hourly infusion rate
recommended by CDSS to
fidence in the strength of the limited available evidence to

adjusted by provider for
% of time UOP CDSS: Hourly infusion rate
make any recommendations on the use of albumin to limit

of 30-50 mL/hour
edema-related complications.
Question 2: Among adults with burns ≥20% TBSA should
albumin be initiated early (<12 hours post burn) or late (after
12 hours post burn) during acute fluid resuscitation to (a) re-
Index; SVRI: Systemic Vascular Resistance Index; TBSA: total body surface area; TPTD: trans-pulmonary thermodilution; UOP: urine output.
duce total fluid resuscitation volume or total crystalloid resus-

citation volume at 24 or 48 hours post burn, (b) increase urine
output, or (c) decrease edema-related complications?
We identified only one study that met criteria for inclusion
Other relevant
Vent-free days
by addressing the PICO question of administering albumin

outcomes
in target
“early” (<12 hours), compared to ”late” (>12 hours).52

Mortality
The ABRUPT study provided essential observational data

to inform the design of the ongoing ABRUPT-2 study
Q7: Computerized Decision Support Software (CDSS) vs. UOP alone for titration of resuscitation
(NCT04356859), but unfortunately, it provides only low-

strength evidence to answer this question. Patients who re-
24-hour crystalloid
PICO-relevant
ceived albumin <12 hours (N = 118) had significantly larger

outcomes
and deeper burns than those given albumin after 12 hours (N

volume
= 135). There was also a critical difference between these 2

groups: up to the point when albumin was started, those that
received early albumin had been administered significantly
more crystalloids and had a significantly higher in-to-out (I:
O) ratio than those who were given albumin late. This creates
Control: N = 38, age 50 ±
21, % TBSA burn 40 ±
± 16, % FT burn 9 (0,
19, % FT burn 12 (0,

70 CDSS: N = 32, age 44 ±
16, % TBSA burn 39
a potential selection bias toward administering albumin earlier

to patients with more extensive injuries who were rapidly con-
17), INHI 31 %
41), INHI 29%

Sample
suming large volumes of crystalloids. Thus, this study cannot

answer the question of early versus late albumin with respect
to any of our specified outcomes. However, one finding
using a linear mixed effect model did show a faster rate of
decline in fluids if albumin is given compared to not giving
it (point estimate −29.52, 95% CI, −24.21 to −34.83, P <
All values shown as mean ± SD or median (IQR).
.001). Thus, one might hypothesize that the sooner albumin

Total
N
is administered, the faster the fluid infusion rate will decline,

potentially leading to less fluid administration. This is the-
oretical, and no firm conclusions can be reached about the
effects of earlier versus later albumin administration from the
Design
ABRUPT study.
Two studies provide additional information, but these were
Table 1. Continued
not included for critical review either because the population

CC
was not adult,67 or there was no comparator.68 A RCT in 46

pediatric patients with burns between 15% and 45% TBSA and
201163
no inhalation injury compared the intervention of giving a

Author
4-hour infusion of 5% albumin once daily for 3 days starting at

Salinas
8-12 hours post burn, with a control group that also received
Table 2. Scores from critical review using method of Law et al.64
Sample Outcomes Intervention Results

Study Liter- Detailed Analysis Clinical

pur- ature De- Justi- Reli- descrip- Contami- Co- Statistical appro- impor- Dropouts Conclusions Total
Study pose review sign Size Details fied able Valid tion nation intervention significance priate tance reported appropriate score
Abeoletta 1 1 CC 30 0.5 1 0.25 0.25 1 0 1 1 1 1 1 0.75 10.75

Chen 0.5 1 CC 34 0.5 1 0.25 0.25 0 0 0 1 1 0.5 1 0.5 7.5
Chung 1 1 CC 52 0.5 1 0.5 0.5 0.5 1 0 1 1 1 1 1 11
Cochran 1 1 CC 202 0.5 1 0.5 0.75 0.5 1 1 1 1 0.5 1 1 11.75
Comish 1 1 CC 91 1 0.5 0.5 0.5 0.5 1 0 1 0.5 0.5 1 0 9
Cooper 1 1 RCT 42 1 1 1 1 0.75 1 1 1 1 0.5 1 0.5 12.75
Du 1 1 CC 30 0.5 1 1 1 0.25 1 1 1 1 0.5 1 0.5 11.75
Flores 1 1 CC 75 0.75 1 0.75 0.75 1 1 0 1 1 0.5 1 1 11.75
Foldi 2009 1 1 RCT 16 1 1 1 1 1 1 1 1 1 0.25 1 0.5 12.75
Foldi 1 1 RCT 30 1 1 1 1 1 1 1 1 1 0.25 1 0.5 12.75
Goodwin 1 0.5 CC 24 0 0.75 0.5 0.5 0 1 1 1 1 0 1 0.5 8.75
Goodwin 1 1 RCT 79 1 1 1 1 0.75 1 1 1 1 1 1 0.25 13
Greenhalgh 1 1 CC 379 0 1 0.5 0.5 0 0 0 1 1 0.5 1 1 8.5
Holm 1 1 RCT 50 0.75 1 1 0.5 1 0.75 1 1 1 1 1 1 13
Kahn 1 1 CC 33 0.75 1 0.5 0.5 1 1 0 1 1 0.5 1 0.75 10.75
Lawrence 1 1 CC 52 0.5 1 0.5 0.5 0.75 1 1 1 1 0.75 1 0.75 11.75
Lin 1 1 CC 80 0.75 1 0.75 0.75 1 1 0 1 1 0.5 1 1 11.75
O’Mara 1 1 RCT 31 1 1 1 1 0.75 1 1 1 1 1 1 1 13.75
Park 1 1 CC 159 0.5 1 0.5 0.5 0.5 0 0 1 0.5 0.5 1 0.5 8.5
Recinos 1 1 RCT 15 0.25 1 0.5 0.5 0.25 1 0.5 0.25 0.25 0.5 1 0.5 8.5
Saitoh 1 1 RCT 36 0.75 0.75 0.75 0.75 1 1 0 1 1 0.5 1 1 11.5
Salinas 1 1 CC 70 0.5 1 1 1 0.5 1 0.5 1 1 1 1 1 12.5
Tanaka 1 1 RCT 37 1 1 0.75 0.75 1 1 1 1 1 1 1 1 13.5
Zhu 1 0 CC 191 0.5 1 0.5 0.5 0 0 0 1 1 0.5 1 0.5 7.5

the daily 4-hour albumin intervention but where the first dose field is strong prospective data for the starting rate of 2ml/
was started after 24 hours.67 Patients in the intervention group kg/%TBSA versus. 4ml/kg/%TBSA.
received significantly less crystalloid over the first 3 days and For this PICO question, 2 studies with moderate-strength
had significantly less “fluid creep,” defined by subjective eval- evidence met criteria for inclusion and review.10,55 The first
uation of edema in unburned tissue and presence of an associ- study was a retrospective analysis of the military’s experi-
ated problem (pulmonary congestion, cardiomegaly, effusion, ence in 52 cases with initiating crystalloids based on 2ml/
deepening of burns, need for escharotomy or fasciotomy, ab- kg/%TBSA (Modified Brooke formula) compared to
dominal compartment syndrome). A secondary analysis found starting with 4 mL/kg/%TBSA burn (Parkland formula).10
that the intervention group had a shorter hospital length of Albumin was recommended if at 12 hours, the total fluids

stay, and that less “fluid creep” associated with the interven- were projected to exceed 6 mL/kg/%TBSA by 24 hours.
tion led to a lower probability of developing an infection.69 It The study had several limitations, largely related to the ret-
is difficult to translate these findings to our question. The pop- rospective design, and conduct under austere battlefield
ulation involved children with a limited range of burn size and conditions in Afghanistan. These include (1) insufficient data
no inhalation injury, and the intervention was somewhat unu- for 58 of 105 patients meeting the inclusion criteria of being
sual in that most providers run continuous albumin infusions evacuated from combat operations with burns >20% TBSA,
over longer periods of time, rather than as daily 4-hour doses. (2) a potential selection bias in favor of the Modified Brooke
Nonetheless, the administration of a single “early” dose of formula, because there was a tendency to use it in patients
albumin appears to have had an important effect. A particu- with bigger and deeper burns and those with more frequent
larly intriguing observation is that the early albumin patients associated injuries, whereas the Parkland formula was used
had less pulmonary edema, whereas in Goodwin et al.’s RCT proportionally more in burns under 40% TBSA and less in
in adults19 (albumin vs. crystalloid alone, discussed in ques- burns over 40% TBSA, (3) a risk of a performance bias as the
tion 1), more lung water was observed in patients in the al- Modified Brooke formula originated in the military, (4) al-
bumin arm, where albumin had been started within 12 hours though albumin was used similarly in both groups, there is
of injury. A retrospective study in adults with burns >20% potential for confounding due to this cointervention because
TBSA including those with inhalation injury, examined a albumin may have exerted more benefit in the more severely
protocol where a 1:1 mixture or 20% albumin and LR was injured Modified Brooke resuscitations. FFP was also used
started within the first 8 hours post burn, then reducing the in both groups in the first 24 hours, (5) all but one patient
albumin concentration as resuscitation proceeded.68 This pro- was male, limiting the generalization of the findings, and (6)
tocol reduced the 24-hour resuscitation volume to 2.58 ml/ the outcome of abdominal compartment syndrome was de-
kg/%TBSA; much less than the expected Parkland value of 4 fined by decompressive laparotomy, which in the absence of
ml/kg/%TBSA burn, but there was no control group where documented abdominal pressures or other diagnostic criteria,
albumin was administered later to serve as a comparator. is to some extent is an operator-dependent measure. The
In situations where albumin is part of the resuscita- second study is a multicenter RCT of 39 adult burn patients
tion plan, (ie, not a rescue situation), we are uncertain which directly compared starting resuscitation with 2 mL/
on whether to start albumin before or after 12 hours to kg/% TBSA burn (Modified Brooke Formula) to starting
reduce the volume of administered fluid, improve urine with 4 mL/kg/%TBSA burn (“Baxter formula”).55 The
output, or decrease edema. Given the uncertainty around study precluded the use of albumin during the first 6 hours
this question, the uncertainty about the undesirable of resuscitation, but both groups did receive albumin and/or
outcome of pulmonary edema related to early albumin FFP during the first 48 hours with a slight tendency to have
provision19 and the overall importance of timing, we rec- administered more FFP to the Modified Brook group in the
ommend that initiation of albumin any time in the first first 24 hours. There was also a small but relevant difference
12 hours preferably be considered in the context of a re- in titration approaches. In both groups, fluids were titrated to
search study. achieve a UOP of 0.5 mL/kg/hour, but in the Baxter group,
Question 3: Among adults with burns ≥20% TBSA, does this was done every 2 hours according to “the treatment
starting acute fluid resuscitation with 2 mL/kg/%TBSA burn policy of the facility,” whereas in the Modified Brooke group,
compared to starting with 4 mL/kg/%TBSA burn (a) reduce this was by a protocol of incremental one-third increases or
total fluid resuscitation volume or total crystalloid resuscitation decreases in the infusion rate. The study’s limitations were (1)
volume at 24 or 48 hours post burn, (b) affect the development of a small sample due to early termination resulting from slow
acute kidney injury, or (c) reduce edema-related complications? enrollment before reaching the planned N of 50 patients, (2)
Numerous studies over the 2000s and 2010s brought cointervention with albumin and FFP with more FFP given
to light the clinical implications of over-resuscitation and in the 2 mL/kg/%TBSA group, (3) a risk of performance
the reality of the “fluid creep” phenomenon.6,8 The totality bias, as titration approaches appeared to be different between
of these findings guided the American Burn Association to groups, and (4) criteria for the outcome of ACS were not de-
change from a resuscitation starting at 4ml/kg/%TBSA burn fined and included ACS as late as 28 days; ACS during the
to a 2ml/kg/%TBSA burn in 2011 (ABLS Course Manual). acute resuscitation would be more relevant.
The existing practice guidelines for acute fluid resuscitation As was the case in question 1, we did not specify mortality
recommend initiating crystalloids at 2 to 4 mL/kg/%TBSA as an outcome for this PICO question. Again, this only reflects
burn.70 All of these studies are a remarkable demonstration the limited scope of the available investigations to answer this
of the power of thoughtful retrospective observation on the question, and not the importance of that outcome. Neither
ability to improve patient care. What remains lacking in the of our 2 included studies found any difference in mortality
between starting resuscitation with 2mL/kg/%TBSA burn randomized-controlled study.31 Of note, these 2 studies
versus 4 mL/kg/%TBSA burn, but as noted, both studies contained common authors from the same institution.
were small and underpowered to reliably assess this outcome. Decreased fluid requirements are the main proposed benefit
With respect to the outcome of resuscitation volumes, both of FFP. Although the retrospective Du et al, study29 is 30 years
studies demonstrated that the 2 mL/kg/%TBSA burn ap- old and at risk of selection and performance bias, significantly
proach reduced total fluid resuscitation volumes at 24 hours decreased total infusion volumes at 24 hours were observed
post burn (Table 1). Only the Saitoh study55 reported fluids in the FFP cohort when compared to the crystalloid cohort.
at 48 hours and found no significant difference in resuscita- There was no difference in urine output at 24 hours between
tion volumes (5.52 ± 2.08 in the 2 mL/kg/%TBSA group groups. Body weight gain was the only edema-related meas-

compared to 6.90 ± 2.37 mL/kg/%TBSA in the 4 mL/ urement taken in the study, which was significantly lower in
kg/%TBSA group, P = .078). It is important to recognize the FFP cohort. Average weight gain in the FFP patients was
that both studies may have had risks of selection and/or per- only 20% and 28% of that gained by the crystalloid patients
formance biases in favor of limiting fluids while using the on post burn days 1 and 2, respectively, indicative of much
Modified Brooke approach. Both studies are also subject to less edema in the colloid-treated patients. However, no other
the potential confounding influence of administering colloids edema-related morbidity outcomes were reported. In addi-
in the first 24 hours. tion, the authors report no observation of early or late pulmo-
With respect to the outcome of AKI, both studies present nary complications in the FFP cohort. However, 2 of the 10
data to suggest no differences in incidence of acute kidney patients died in the FFP cohort. These patients were described
injury between the 2 approaches. Chung et al.10 show rates as having “severe smoke inhalation injury.” Considering the
of AKI on arrival to the US Army Burn Center after evac- potential safety issue regarding FFP and Transfusion Related
uation from the battlefield at 19% in the 2 mL/kg/%TBSA Acute Lung Injury (TRALI) to be discussed at the end of this
group compared to 10% for the 4 mL/kg/%TBSA group (P section, this observation is relevant. It is conceivable that any
= .33). An explicit statement of AKI definition was not pro- pulmonary dysfunction related to these 2 deaths could have
vided. Saitoh et al. utilized KDIGO guidelines and presented been related to TRALI (which was an unrecognized entity
findings at 24 and 48 hours with no differences between 2 30 years ago) rather than, or in combination with inhalation
mL/kg/%TBSA and 4 mL/kg/%TBSA.55 Of interest was injury.
that in a subanalysis of patients with burns >40% TBSA, UOP The RCT by O’Mara et al.31 was a small but appropriately
tended to lag in the Modified Brooke approach in the first powered study which demonstrated significantly less fluid
8 hours of resuscitation, but eventually picked up by 24-48 administered in the first 24 hours with improved physiologic
hours. parameters such as decreased peak inspiratory pressure (PiP),
Finally, with respect to the outcome of edema complications, decreased intra-abdominal pressure and improved correc-
neither study found any clinically meaningful differences in tion of base deficit with use of FFP compared to crystalloid
measures such as oxygenation or development of ACS. The alone. Urine output was similar between groups and over the
available data are limited, and the outcomes as described standard target of 0.5 mL/kg/hour. Also at 24 hours, FFP
were somewhat unreliable, because data regarding IAP, limb resuscitation was associated with a lower peak intra-abdominal
compartment syndrome, and ocular complications are not pressure (IAP) of 16.4 ± 7.4 compared to the crystalloid co-
provided. hort at 32.5 ± 9.5. Both groups took over 68 hours to reach
We recommend that clinicians consider starting acute their peak IAP. There are no outcomes reported that relay
fluid resuscitation using 2 mL/kg/%TBSA burn to re- whether a decreased PiP was associated with improved venti-
duce the total volume of resuscitation fluids. An impor- lation or oxygenation, but almost certainly this was related to
tant consideration is that in both studies that informed lower intra-abdominal pressures. Similar to the Du et al. study,
this recommendation,10,55 colloids were coadministered decreased weight gain was observed in the FFP cohort. Thus,
in some patients. We also emphasize that this recommen- less fluid translated to relatively objective improvements in
dation suggests only the initial fluid rate, and that titra- edema-related outcomes such as weight gain, intra-abdominal
tion based on the patient’s response must follow. We are pressures, and peak airway pressures.
unable to make any recommendation on use of 2 mL/ There are 2 potential safety issues related to using FFP
kg/%TBSA burn to reduce edema-related complications for acute burn shock resuscitation. The first is TRALI which
and we suggest that more research is needed to assess the continues to be the leading cause of transfusion-related
effect of this approach on the development of AKI. death.71 The incidence of TRALI and delayed TRALI is vari-
Question 4: Among adults with burns ≥20% TBSA, should able, and these syndromes are likely under-reported, but these
fresh frozen plasma (FFP) be used during acute fluid resusci- dose-dependent events may occur in up to 3% and 25%, respec-
tation compared to using crystalloids alone to (a) reduce total tively, of critically ill patients who receive blood products.72,73
fluid resuscitation volume or total crystalloid resuscitation The risk of TRALI during acute burn resuscitation with FFP
volume at 24 or 48 hours post burn, (b) increase urine output, or is unknown and we are aware of only one report describing
(c) decrease edema-related complications? this.30 The use of male-only donors for plasma products and
For this question, our search identified 2 studies29,31 which possibly the use of pathogen reduced plasma through solvent-
met our inclusion criteria of comparing fresh frozen plasma detergent (SD plasma) preparation74 may help to reduce the
(FFP) to crystalloid alone and examined at least one of our de- risk of TRALI. The ongoing Plasma ResuscitatiOn WithOut
fined outcomes. One investigation29 was a moderate-strength Lung Injury (PROpOLIs) study NCT 04681638 will ad-
case-control study, and one study was a high-strength dress much of this uncertainty. The second safety issue is the
risk of disease transmission from blood-borne pathogens. of 66 mg/kg/hour over 24 hours) versus low-dose vitamin C
Fortunately, newer pathogen-reduced preparations of human (single 3.5 gm infusion) allowed for “colloid” administration
plasma may prevent transmission of HIV, hepatitis B and C if resuscitation targets could not be met with fluid alone and
but not hepatitis A or some encapsulated viruses, or prion had planned to stop the vitamin C infusion for hypotension
diseases.74 or tachycardia as part of the protocol. (While no ascorbic acid
We recommend that fresh frozen plasma (FFP) be used infusions were stopped, the use of this safety feature raises the
in acute burn shock resuscitation only in the context of question of whether the investigators were anticipating hypo-
a research study. Currently, there is insufficient evidence volemia effects related to the vitamin C infusion).39
to make a recommendation for FFP to affect any of our Among our included studies, there were no differences in

stated outcomes, but we believe there is a large potential clinical outcomes with the use of HDVC compared to crys-
for reducing uncertainty about the desirable and undesir- talloid alone (Table 1), except in the RCT by Tanaka et al.36
able effects of FFP through further research. That study demonstrated that the HDVC patients had less
Question 5: For adult patients with a ≥ 20% TBSA burn in- acute weight gain, less measured soft tissue edema, and pos-
jury, does administration of high dose (66 mg/kg/hour) ascorbic sibly less pulmonary edema as measured by the surrogate
acid (vitamin C), compared to not using high dose ascorbic acid, markers of PaO2/FiO2 ratio over the first 96 hours and du-
while providing crystalloids alone during acute fluid resuscita- ration of mechanical ventilation.36 Lin et al. observed the op-
tion (a) reduce total crystalloid resuscitation volume at 24 or posite: median ventilator days actually tended to be higher in
48 hours post burn, (b) increase urine output, or (c) decrease the HDVC-treated patients than in controls (11 vs. 5 days, P
edema-related complications? = .07).37
For this question, our search identified four studies36–38,56 Recently, a safety concern has been raised with respect to
which met our inclusion criteria of comparing high-dose vi- administration of HDVC. Oxaluria and deposition of calcium
tamin C (HDVC) at 66 mg/kg/hour to crystalloids alone, oxalate crystals in the renal tubules leading to nephropathy
with examination of at least one of our defined outcomes. have been observed in both non-burn75 and burn patients40
Three investigations were case-controlled retrospective receiving very high doses of ascorbic acid. Among our in-
studies of moderate strength,37,38,56 while one study pro- cluded studies, Lin et al. reported more frequent renal failure
vided stronger evidence in the form of a pseudo-randomized requiring dialysis in HDVC-treated patients compared to
controlled trial.36 controls (23% vs. 7%, P = .06) with an independent associa-
Sparing of resuscitation fluids is the main purported benefit tion between HDVC with development of acute renal failure
of HDVC. The retrospective studies found either no differ- requiring dialysis (OR 5.4 95%CI, 1.1-26).37 While not
ence37 or a significant reduction in 24-hour fluid resuscitation specified, it appears the dialysis occurred at any time during
volumes.38,56 Unfortunately, all 3 studies were confounded by the hospitalization period, rather than during the resuscitation
the coadministration of colloids, without adequate description phase. Flores et al. reported no differences in AKI (KDIGO
of whether this was controlled or similar between groups. The criteria) during the resuscitation phase.56 Kahn et al. also re-
addition of colloids could have a significant effect on resusci- ported no differences in renal function, but a definition or
tation fluid volume. In contrast, the study by Tanaka et al.36 criteria for the diagnosis of AKI were not provided.38 A retro-
did show a significant reduction in 24-hour fluid volumes. spective study on early AKI following major burns identified
While this study is weakened by a small sample size and risk of an association with HDVC use during resuscitation (OR 5.5,
performance bias in fluid administration and titration between 95% CI, 1.2-25.1).41
study arms due to its open-label and pseudo-randomized de- Finally, questions persist surrounding the dose of HDVC.
sign, it provides the strongest evidence we have that HDVC While all our included studies provided 66 mg/kg/hour of
has a fluid-sparing effect. It provides human validation of ascorbic acid, only one study reported the total administered
observations from preclinical animal studies. dose (170 gm).56 Click or tap here to enter text. Of interest,
It was recognized from preclinical studies that HDVC has Nagal et al.39 observed that the use of HDVC (66 mg/kg/
a potent diuretic effect. All 4 of our included studies36–38,56 hour) compared to a 3.5 gm/day IV infusion produced sig-
reported increased urinary output when HDVC was nificantly more diuresis (1.2 vs. 0.8 mL/kg/hour) but found
administered (Table 1). One study which we did not include, no statistically significant or clinically relevant differences in
because the comparator was a lower dose of ascorbic acid and 24-hour crystalloids, 24-hour or 24-72 hours total fluids, de-
not crystalloid alone39 found a dose-dependent increase in velopment of AKI or use of RRT, length of stay or mortality.
UOP when higher doses (66 mg/kg/hour) of ascorbic acid A Japanese national database sample76 compared patients who
were administered. The diuresis produced by HDVC has 2 received either ≥10 gm (n = 157, median dose 50 gm) or
consequences. The first is distortion of the hourly UOP as a ≥24 gm (n = 127, median dose 63 gm) of ascorbic acid in
titration endpoint. The second is the potential for dehydration the first 48 hours with propensity score matched controls (n
due to the osmotic diuresis. Kahn et al. commented that sev- = 628 and n = 508, respectively). There were no differences
eral patients receiving HDVC had elevated hematocrits and in administered fluids or survival using the 24 gm threshold,
signs of hypovolemia without decreased UOP in some cases, but at the 10 gm threshold, the vitamin C patients received
possibly a sign of dehydration from osmotic diuresis. These significantly more fluid at 24 and 72 hours, but paradoxi-
patients received additional FFP.38 Patients in both the crystal- cally had significantly lower in-hospital mortality. Overall, it is
loid and vitamin C arms in 2 of our included studies received not clear whether there is an optimal dose for vitamin C and
25% albumin37 or “colloid”56 potentially to counteract hypo- whether such a dose might confer improvements in outcome.
volemia. A study of high-dose vitamin C (continuous infusion While not a study specifically on acute fluid resuscitation in
the first 48 hours, further understanding regarding dose and group. The multiorgan dysfunction score was significantly
outcome may arise from the ongoing vitamin C in thermal in- lower in the second 24 hours after presentation in the ITBVI
jury (VICToRY) pilot trial (NCT04138394) which compares group, but after 1 week, this difference appeared to resolve,
the effect of 200 mg IV ascorbic acid/kg/day for 96 hours to and overall multiple organ failure during the stay was the same
placebo, on the composite outcome of persistent organ dys- in both groups. Mortality, duration of mechanical ventilation,
function and all-cause mortality. and incidence of sepsis were not different between groups,
We are unable to form any recommendation for high- and neither group had any incidence of intra-abdominal com-
dose vitamin C (66 mg/kg/hour) to reduce total crys- partment syndrome.
talloid resuscitation volumes, increase urine output, or Retrospective data review by Zhu et al.62 evaluated the

decrease edema-related complications. While it appears utilization of Pulse index Continuous Cardiac Output
that high-dose vitamin C promotes diuresis and may re- (PiCCO) analysis. The study was rated at low-strength due
duce resuscitation volumes, this is closely balanced by to risks of performance bias, intervention contamination,
the trade-offs of distortion of urine output as a titration and cointerventions. The control group was managed using
endpoint, possible dehydration from osmotic diuresis, standard fluid resuscitation and conventional monitoring,
uncertainty about dose, and the unknown risk of oxalate while the study group had additional data available from the
nephropathy. PiCCO system. While overall resuscitation volumes were
Question 6: Among adults with burns ≥20% TBSA, during significantly different between the groups, this was driven
acute fluid resuscitation should (a) CVP, (b) transpulmonary by differences in colloid administration; crystalloid volumes
thermodilution (TPTD), or (c) stroke volume variation(SVV) were the same at both the 24 hours (1 mL/kg/%TBSA, a
or pulse pressure variation (PPV) from arterial waveform ana- third lower than the stated Third Military Medical University,
lysis be used to titrate resuscitation fluids, compared to using TMMU formula) and 48-hour mark (0.75 mL/kg/%TBSA,
hourly urine output either alone or in conjunction with “con- on target for the stated TMMU formula). They did identify
ventional” endpoints such as heart rate, blood pressure, serum that ARDS incidence was worse in the control group, and
lactate, and arterial base deficit, to (a) reduce total fluid resus- multivariate analysis suggested that PiCCO monitoring might
citation volume or total crystalloid resuscitation volume at 24 or decrease the incidence. In addition, length of stay was shorter
48 hours post burn or (b) decrease edema-related complications? in the monitored group, which they suggested was an out-
Fluid resuscitation in critical care has been augmented come potentially related to fluid overload.
over the years with technology providing more insight into Chen and colleagues58 used PiCCO to assess global end di-
minute-to-minute patient physiology. For this question, we astolic volume index (GEDVI), EVLWI, and systemic vascular
considered invasive or semi-invasive resuscitation monitoring resistance index (SVRI) in patients with massive burns (80%
adjuncts compared to either urine output alone (the gold TBSA or greater). This study was also rated as low-strength
standard for burn resuscitation) or urine output in conjunc- evidence due to risks of selection and performance bias. Mean
tion with other more routinely available adjuncts. Six studies fluid volumes were lower when PiCCO was used (3.3 mL/
were identified that met inclusion criteria (Tables 1 and 2). kg/%TBSA vs. 3.7 mL/kg/%TBSA). They identified im-
Three were reported as randomized control studies,59–61 all provement in markers of oxygen delivery and improved gas
with high strength, while the other 3 were low to moderate exchange in the lung with the use of PiCCO, but no difference
strength case-control studies.57,58,62 in renal end organ perfusion as measured by urine output.
Holm and colleagues compared use of the traditional They were unable to comment on mortality differences and
Baxter formula (4 mL/kg/%TBSA) against transpulmonary did not comment on local limb perfusion issues.
thermodilution (double indicator, thermal, and dye).61 They Aboelatta57 looked at a cohort of patients using
targeted intrathoracic blood volume index (ITBVI) cardiac transpulmonary thermodilution (PiCCO) versus a modified
index (CI) and extra-vascular lung water index (EVLWI). Parkland formula of 3 mL/kg/TBSA and urine output with
Control patient management was modified by use of cen- CVP. They definitively demonstrated higher fluid administra-
tral venous pressure and mean arterial pressure in addition to tion in the first 24 hours using PiCCO rather than conven-
urine output. While fluid administration volumes were signifi- tional markers (5.4 mL/kg/%TBSA vs. 4.6 mL/kg/%TBSA),
cantly higher in the invasive monitoring group, there were no with higher UOP values (2.25-3.6 mL/kg/hour vs. 1.1-1.8
differences in mechanical ventilation, acute renal failure, or mL/kg/hour). Resuscitation in the PiCCO arm was stopped
multiple organ failure. No pulmonary edema was noted in ei- early given significant tissue edema; pulmonary edema and
ther group. Two patients had catheter-related complications. compartment syndrome occurrence were not recorded.
Foldi et al., in 2 high-strength studies,59,60 evaluated Overall, the data from the higher strength RCTs59–61 and
intrathoracic blood volume index (ITBVI) obtained by TPTD one moderate strength retrospective study57 suggest equiv-
versus hourly urine output. They also identified that more alent to higher fluid resuscitation volumes with an invasive
fluid was given in the invasive monitoring group (5.5 mL/ monitoring device-driven resuscitation. Edema complications
kg %TBSA vs. 4.3 mL/kg/%TBSA) in the first 24 hours, but were not significantly impacted by the use of a monitoring de-
that when the resuscitation goal objective of ScvO2 of >70% vice. However, it is possible that by adjusting the physiologic
was utilized as the endpoint of resuscitation, the same amount target of the resuscitation59,60 the duration of burn shock re-
of fluid volume was required in both groups (6.1 mL/ suscitation might be shortened.
kg/%TBSA vs. 6.3 mL/kg/%TBSA). Interestingly, the time We do not recommend the use of transpulmonary
to achieving complete resuscitation was different between thermodilution-derived variables (eg, ITBVI, GEDVI,
groups, 35 hours in the HUO group vs 28 hours in the ITBVI CI, or EVLWI) to reduce total resuscitation fluid
volumes or decrease edema-related complications. Due to mentions that UOP rates within target were up to 20% higher
a paucity of evidence, we were unable to make any rec- “when providers followed the system recommendation.”
ommendation regarding use of SVV or PPV on either of Most recently, CDSS was evaluated in 5 burn US centers,
these outcomes. combining retrospective data and prospectively obtained ob-
Question 7: Among adults with burns ≥20% TBSA, should servational data.77,78 This study was not included for critical
computerized decision support software (CDSS) compared to review because no comparisons to not using CDSS were made.
using hourly urine output alone be used to titrate acute resus- Across all 285 patients, clinicians agreed with the computer’s
citation fluids to (a) reduce total fluid resuscitation volume or recommended infusion rate, within ± 20 mL/hour, 72% of
total crystalloid resuscitation volume at 24 or 48 hours post burn the time, but this ranged between 54% and 96% between

and (b) decrease edema-related complications? centers. The mean 24-hour crystalloid volumes ranged
For this question, we found a single high-strength study63 across centers from 3.1 mL/kg/%TBSA burn to 4.5 mL/
that met the inclusion criteria of comparing use of CDSS to kg/%TBSA burn, while total administered 24-hour volume
not using CDSS. This study describes the validation of a com- ranged from 3.5 to 5.3 mL/kg/%TBSA burn. This is lower
puterized decision software system (CDSS) developed at the than the average resuscitation volume of 5.2 mL/kg/%TBSA
US Army Institute of Surgical Research (USAISR) and the burn identified in a quantitative review of fluid resuscitation
University of Texas Medical Branch (UTMB). The CDSS involving 3196 patients from 48 studies published over the
was originally designed for combat casualties, with the antic- past 30 years.79 A total of 146 of the 285 patients followed the
ipation that non-burn experienced providers would provide CDSS recommendations (defined as administering a fluid rate
initial burn stabilization close to the point of injury and con- within ± 20 mL/h of the recommended rate, 83% of the time
tinue through transport to a definitive care facility. The bed- in the first 24 hours, ie, in 20 of the first 24 hourly decisions).
side provider inputs the patient’s weight, TBSA burn extent, In those that followed CDSS, the 24-hour crystalloid volume
time since injury, and fluids that had been administered prior was 4 ± 1.6 mL/kg/%TBSA burn, and not significantly lower
to CDSS initiation. The provider then sets the initial fluid rate that the 4.1 ± 1.9 mL/kg/%TBSA burn administered to non-
(based on available resuscitation formulae) as well as the urine followers.77 The interpretation of all fluid volumes, while using
output goal for each individual resuscitation. Every hour, the CDSS, should also consider that colloids were administered to
CDSS prompts manual input of urine output (UOP) for the some patients. While these were included in the reported total
last hour by the bedside clinician (most commonly a nurse). resuscitation volume, colloids may have a fluid sparing effect
Using linear regression of UOP trend over the previous 3 (see questions 1 and 4), and this potentially confounds the ef-
hours, the CDSS provides the clinical team a recommenda- fect of CDSS titration on resuscitation volumes.
tion for crystalloid rate over the next hour. This strategy is None of the existing studies has specifically or reliably
termed decision-support as the bedside clinician is free to ac- evaluated edema-related outcomes. Salinas’ 2011 study63 re-
cept or modify the fluid rate until check-in at the next hour. ported secondary clinical outcomes, including an increased
The CDSS also only makes a recommendation on crystalloid in number of ICU-free days, ventilator-free days, and lower
infusion rate, even though the provider can log data for all mortality (29% vs. 44%, P < .05) with CDSS strategy. Given
fluid types and routes administered (crystalloid, colloid, in- the mechanistic link between total fluid administration and
travenous, enteral). Following its initial development, CDSS edema formation, CDSS may possibly reduce edema-related
technology is now provided using an FDA-approved device complications, but this hypothesis remains to be proven, and
used in many US burn centers under the trade name Burn no definitive conclusions on clinical outcomes can be made
Navigator. from the Salinas study.
Salinas and colleagues retrospectively evaluated the utility The CDSS prospective observational trial recorded de-
of CDSS in 32 adults with burns ≥ 20% undergoing acute fluid compression procedures performed for both prophylactic and
resuscitation with at least 24 hours of CDSS recommendations therapeutic purposes and found no differences in limb, ab-
in the first 48 hours post burn at a single center compared to dominal, or orbital compartment syndromes between those
38 historical control patients resuscitated through traditional/ that did or did not follow CDSS recommendations.77,78
manual hourly urine output recording.63 For the outcome of We make a weak recommendation for clinicians to con-
fluid resuscitation volumes, CDSS resuscitation resulted in sider the use of CDSS to reduce total resuscitation fluid
24-hour total resuscitation volume of 4.2 mL/kg/%TBSA volumes, but we are unable to make any recommendation
burn which was significantly lower compared to 6.5 mL/ on use of CDSS to reduce edema-related complications.
kg/%TBSA burn for patients resuscitated by the traditional The panel was concerned about the potential for loss of
method. Notably, UOPs for CDSS patients were significantly frequent bedside clinical patient assessment and critical
more frequently within the set target UOP goals over the first decision making by clinicians using CDSS. The benefit of
48 hours (31% vs. 23% of the time, respectively), highlighting CDSS probably, but not certainly, outweighs this unde-
the utility of CDSS in reducing hourly variations in fluid rates sirable effect.
thanks to a “tighter” titration. Notwithstanding the risk of bias Question 8: Among adult patients with ≥20% TBSA burn
in this retrospective study that used historical controls, this is injury undergoing acute fluid resuscitation who require a vaso-
the only and strongest evidence available comparing CDSS pressor for hypotension, should norepinephrine or vasopressin be
to “usual titration” not using CDSS. Another limitation is the first administered vasopressor to (a) reduce 28-day mortality
that while at least 24 hours of recommendations were needed and (b) reduce acute kidney injury?
to be included in the intervention group, it is not clear how For this question, our search did not find any studies which
often the recommendations were followed. The discussion met our inclusion criteria of comparing norepinephrine and
vasopressin with the defined outcomes of lower 28-day mor- with norepinephrine. The Risk Injury Failure Loss End Stage
tality and a lower incidence of acute kidney injury. (RIFLE) criteria were used as the outcome measure. For
Despite appropriate resuscitative volume administration, patients in the Risk category, there was a lower incidence of
refractory vasoplegia can persist from systemic inflamma- progression to failure or loss for patients treated with vaso-
tion secondary to a severe (≥20% TBSA) burn injury causing pressin. Also, in the risk category, compared to the norep-
hypotension.80 In order to avoid the consequences of over- inephrine group, serum creatinine lowered over the study
resuscitation, vasoactive agents are administered to optimize period in the vasopressin-treated patient. For the other RIFLE
blood pressure. In an animal burn injury model, splanchnic categories, there were no differences in progression to failure
blood vessels showed increased responsiveness to vasopressin or loss or differences in serum creatinine.88 Another large

compared to phenylephrine in the first 24 hours following multicenter double-blind randomized study compared kidney
burn injury.81 During Operation Iraqi Freedom, the US mil- failure-free days between patients with septic shock treated
itary developed a resuscitative guideline in burn-injured mil- with vasopressin or vasopressin and hydrocortisone with
itary personnel undergoing resuscitation for burn shock to patients treated with norepinephrine or norepinephrine and
avoid consequences of over-resuscitation. In situations when hydrocortisone. Kidney failure was defined as Acute Kidney
the mean arterial pressure is ≤55 mm Hg, and urine output Injury Network Stage 3. The study found that was no differ-
is inadequate, vasopressin (0.04 units/min) infusion is the ence in kidney-free days between any of the groups; however,
first vasoactive agent initiated. If hypotension and inadequate there were fewer patients requiring renal replacement therapy
urine output persists despite a central venous pressure of 8-10 in the vasopressin groups.89
mm Hg, then norepinephrine is added as a second agent.82 In Due to the paucity of data about the benefit and risk of nor-
contrast, an international survey of intensivists, 80% of those epinephrine versus vasopressin, we cannot make a recommen-
surveyed would use norepinephrine, as the primary vasoactive dation of which vasopressor to use during burn resuscitation.
agent during burn shock resuscitation.83 A recent systemic re- Due to a complete absence of evidence, the panel is un-
view of the use of vasoactive agents during initial burn resusci- able to form any recommendation on whether to start
tation found only 2 studies that addressed the potential harm norepinephrine or vasopressin if a vasopressor is required.
and benefit of vasoactive agents during burn resuscitation.84 Question 9: Among adults with burns ≥20% TBSA, during
One study is a retrospective review of 16 patients who re- acute fluid resuscitation, should early continuous renal replace-
ceived vasopressors. Norepinephrine was the first agent used ment therapy (CRRT) without fluid removal be initiated,
in 15 of the patients, and phenylephrine was used first in one compared to not initiating CRRT to (a) reduce total fluid
patient.43 The other study is an abstract of a retrospective re- resuscitation volume or total crystalloid resuscitation volume
view of 20 patients in which vasopressors were administered at 24 and 48 hours post burn and (b) decrease edema-related
during resuscitation. The vasopressor was not identified in the complications?
study.84 In both reviews, older age was associated with initia- We did not identify any studies that compared early CRRT
tion of vasopressors. to not using early CRRT as an adjunct during acute burn
In the non-burn literature, there are studies comparing shock resuscitation. Continuous venovenous hemofiltration
the efficacy and benefits of norepinephrine and vasopressin (CVVH) allows for clearance by diffusion of solutes across
during resuscitation and shock. A double-blinded prospective the column’s membrane. In this way, a convection process
randomized study of trauma patients undergoing resuscitation allows for removal of molecules based on the characteris-
randomized adult patients to either placebo or vasopressin tics of the membrane. In most cases, this allows removal of
infusion. Vasopressin or placebo was initiated if the patient water-soluble middle molecular weight proteins (5-50 kDa)
had a systolic blood pressure ≤90mm Hg. The patients in the such as cytokines.90 A burn is known to have a profound in-
vasopressin group required significantly less volume of fluid flammatory process mediated in part by a damage-associated
during the first 120 hours after admission.85 A multicenter molecular patterns (DAMPs) and pathogen-associated mo-
double-blind randomized control study compared 28-day lecular patterns (PAMPs) and the resultant cytokine storm.
mortality in patients with septic shock who treated with ei- Treatment methods to remove these mediators are promising
ther vasopressin or norepinephrine. In this study of 778 conceptual approaches in the care of severely burned patients.
patients, overall, there was no difference in 28-day mortality In addition, the rate or “dose” of convection can be increased
between the vasopressin (35.4%) and norepinephrine group or decreased to the desired effect. Typical levels will approxi-
(39.3%). There was a significant reduction in mortality in mate 20 mL/kg/hour, high-volume hemofiltration (HVHF)
the less severe septic shock group for patients treated with is typically described around 70-90 mL/kg/hour.90 These
vasopressin (26.5%) compared with those treated with nor- approaches have been advocated in alternative inflammation-
epinephrine (35.7%).86 Another study of patients with septic based disease processes such as ARDS, pancreatitis, and sepsis.
shock randomized to either vasopressin or norepinephrine The literature in these diseases does suggest a mortality ben-
also showed no difference in mortality. However, surviving efit with HVHF (RR = 0.88, 95%CI, 0.81-0.95) The sec-
patients treated with vasopressin had significantly lower cyto- ondary outcomes suggest decreased level of plasma cytokines,
kine levels in the first 24 hours after infusion compared to the with higher mean arterial pressures and decrease heart rates in
norepinephrine group.87 the HVHF groups.91 Data for CRRT-HVHF are more limited
For the outcome of renal failure incidence, a multicenter in burn care. We benefit from the work of the Randomized
randomized blinded study of 778 patients compared the inci- controlled Evaluation of High-Volume hemofiltration in
dence of acute kidney injury (28 day) during septic shock be- adult burn patients with Septic shock and acUte kidney in-
tween patients treated with vasopressin versus patients treated jury (RESCUE) investigators for their work on the use of
CVVH-HVHF.44,92 The authors present promising results et al.96 measured IOPs and found that major burn patients
with HVHF decreasing vasopressor dependency index at 48 undergoing bilateral lateral canthotomy had maximal IOPs
hours comparted to baseline, and a decreased multiple organs ranging from 54 to 90 mmHg while those who did not un-
dysfunction syndrome score at 14 days. A limitation for the dergo canthotomy largely had peak IOPs of 23.5 mmHg
applicability of this study is all patients were past the first 48 or less. One recent retrospective analysis recommended
hours of resuscitation, as such no statement to fluids needed monitoring IOP in a variety of scenarios: presence of deep
or edema-related complications were presented. Additional periorbital burns, cumulative 24-hour fluids of 200 mL/kg, or
work from the RESCUE Investigators provide further evi- presence of proptosis.97 Another study identified large surface
dence for the safety of renal replacement therapy in burn44 and area burns, reaching the Ivy Index, and severe facial burns as

suggest that CVVH as a preferred mode of therapy conveys a potential risk factors for orbital compartment syndrome.98 The
survival benefit for patients requiring vasopressors. optimal timing of IOP measurement and its role in preventing
Despite the growing literature for the use of CVVH in burn orbital compartment syndrome, however, remain unclear.
injury, for this question, no articles were identified which met While hyperlactatemia during acute burn shock elevation
criteria for inclusion and review. confers a poor prognosis,99,100 the use of the serum lactate
We are unable to form any recommendation regarding level as a titratable endpoint during burn resuscitation is not
the use of early CRRT during acute burn shock resusci- well understood. Studies which have shown that resuscitation
tation to reduce total resuscitation fluid volumes or de- directed at improving the cardiac index is correlated with a
crease edema-related complications. decline in the serum lactate101 lead us to infer that the oppo-
Question 10: Among adults with burns ≥20% TBSA, should site approach of resuscitating to lower the serum lactate would
(a) intra-abdominal pressure(IAP), (b) Intra-ocular pressure be associated with improving hemodynamic parameters.
(IOP), (c) serum lactate (L), or (d) arterial base deficit be However, definition of the optimal use, timing, and frequency
monitored during the first 48 hours post-burn compared to not of lactate measurements during resuscitation remains elusive.
monitoring IAP, IOP, L, and BD, to (a) reduce total fluid re- Typically, lactate levels are used in combination with other
suscitation volume or total crystalloid resuscitation volume at 24 endpoints like MAP and UOP, and we were unable to find
or 48 hours post burn or (b) reduce the incidence of abdominal any studies which specifically evaluated lactate as an endpoint
compartment syndrome or (c) orbital compartment syndrome? compared to not using it. We encountered a similar problem
We did not identify any studies that specifically compared with evaluating the arterial base deficit (BD) as a titration end-
routine monitoring of intra-abdominal or IOPs or serum lac- point to affect any of our specified outcomes. Like the serum
tate or arterial base deficit to not monitoring these parameters, lactate level, persistent elevation of the BD during burn shock
in order to reduce burn resuscitation fluid volumes or the inci- resuscitation is associated with worse outcomes.99,102,103 The
dence of abdominal or orbital compartment syndromes. BD is a global but non-specific marker of acidemia, and it may
High-volume crystalloid resuscitation of major burns may not correlate with the serum lactate.104 Once again, we found
result in complications including intra-abdominal, orbital, and no studies that evaluated the BD compared to not using it
extremity compartment syndromes. Patients most at risk for during acute burn shock resuscitation.
these complications, of which abdominal compartment syn- We recommend selective monitoring of IAP and
drome (ACS) is the most widely reported, generally have had IOP but not routine monitoring in every resuscitation.
aggressive fluid resuscitation. Suggested markers of high- For IAP monitoring, selective situations would include
volume fluid resuscitation requiring vigilance include the Ivy patients with massive burns, actual or projected 24-hour
Index (250 mL/kg over 24 hours)92 or the “runaway resusci- fluid volumes approaching 6 mL/kg/% TBSA burn or
tation” (6 mL/kg/TBSA over 24 hours).93 250 mL/kg, or clinical evidence of evolving ACS. Some
The optimal frequency of measuring either abdominal or clinicians may wish to follow the WSACS guidelines as
ocular pressure is not defined. Diagnosis of ACS is aided by described earlier. For IOP monitoring, selective situations
the finding of intra-abdominal pressure (IAP) greater than 20 would include actual or projected 24-hour fluid volumes
mmHg with end-organ failure, measured by transducing uri- approaching 6 mL/kg/% TBSA burn or 250 mL/kg,
nary bladder pressure through an indwelling Foley catheter presence of deep extensive periorbital burns regardless of
or with commercially available products.94 The Abdominal the total burn size or fluid volume administered, or prop-
Compartment Society (formerly the World Society of the tosis. The panel was unable to make a recommendation on
Abdominal Compartment Syndrome, www.WSACS.com)95 has routine serial measurement of the serum lactate (L) and
developed an algorithm that recommends measuring abdom- arterial base deficit (BD) in all acute burn resuscitations
inal pressures by urinary bladder pressure transduction every 4 to affect any of our defined outcomes. Serial monitoring
to 6 hours in patients with IAP >12 mmHg, and at least every of L and BD should be used selectively by clinicians.
4 hours in patients with an intra-abdominal pressure of >20
mmHg without new end organ dysfunction (www.WSACS. OPPORTUNITIES FOR FURTHER
com).96 There are no data specific to burn resuscitation, how- RESEARCH
ever, to recommend this frequency or to demonstrate the role
of routine measurement in preventing abdominal compartment The investigator panel noted and was dismayed that many
syndrome or in influencing the volume of resuscitation. studies on acute fluid resuscitation lacked basic and relevant in-
Diagnosis of orbital compartment syndrome, while often formation on parameters such as full thickness burn size, pres-
made clinically, can be augmented by use of ocular pressure ence of inhalation injury confirmed by bronchoscopy, pre-burn
monitoring. Normal IOP is less than 20 mmHg. Sullivan center fluid volumes, indexing of total resuscitation volumes at
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American Burn Association Clinical Practice Guidelines On Burn Shock Resuscitation

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American Burn Association Clinical Practice Guidelines On Burn Shock Resuscitation

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ABA GUIDELINES

American Burn Association Clinical Practice Guidelines on

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Key words: burns; shock; fluid resuscitation.

In 2020, the American Burn Association (ABA) began a

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Q1: Albumin vs. crystalloid

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Total PICO-relevant Other relevant

cantly greater in colloid vs. crystalloid

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(colloids used in 41% post

Q3: 2 mL/kg/%TBSA burn Vs. 4 mL/kg/%TBSA burn

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Total PICO-relevant Other relevant

22, %TBSA burn 30 day 7 kg/%TBSA burn, fluid

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Total PICO-relevant Other relevant

Q5: High dose ascorbic acid vs. no ascorbic acid

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Total PICO-relevant Other relevant

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Total PICO-relevant Other relevant

(First Affiliated Hospital of

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Total PICO-relevant Other relevant

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albumin on mortality. This approach using pooled data from

trol 6.5 ± 4.1 mL/kg/%TBSA burn (P <

CDSS vs. 23% in control (P < .05).

termined that it was unlikely that albumin or crystalloid use

CDSS (P < .05)

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larger burns, and weaker for patients with smaller burns.

target UOP 30-50 mL/hour

ceiving escalating amounts of crystalloids. We have low con-

Both groups resuscitated with

fidence in the strength of the limited available evidence to

make any recommendations on the use of albumin to limit

duce total fluid resuscitation volume or total crystalloid resus-

by addressing the PICO question of administering albumin

“early” (<12 hours), compared to ”late” (>12 hours).52

The ABRUPT study provided essential observational data

(NCT04356859), but unfortunately, it provides only low-

ceived albumin <12 hours (N = 118) had significantly larger

and deeper burns than those given albumin after 12 hours (N

= 135). There was also a critical difference between these 2

19, % FT burn 12 (0,

a potential selection bias toward administering albumin earlier

41), INHI 29%

suming large volumes of crystalloids. Thus, this study cannot

.001). Thus, one might hypothesize that the sooner albumin

is administered, the faster the fluid infusion rate will decline,

not included for critical review either because the population

was not adult,67 or there was no comparator.68 A RCT in 46