Romanowski and Palmieri Burns & Trauma (2017) 5:26

DOI 10.1186/s41038-017-0091-y

REVIEW Open Access

Pediatric burn resuscitation: past, present,

and future
Kathleen S. Romanowski1* and Tina L. Palmieri2,3

Abstract
Burn injury is a leading cause of unintentional death and injury in children, with the majority being minor (less
than 10%). However, a significant number of children sustain burns greater than 15% total body surface area
(TBSA), leading to the initiation of the systemic inflammatory response syndrome. These patients require IV fluid
resuscitation to prevent burn shock and death. Prompt resuscitation is critical in pediatric patients due to their
small circulating blood volumes. Delays in resuscitation can result in increased complications and increased
mortality. The basic principles of resuscitation are the same in adults and children, with several key differences.
The unique physiologic needs of children must be adequately addressed during resuscitation to optimize
outcomes. In this review, we will discuss the history of fluid resuscitation, current resuscitation practices, and
future directions of resuscitation for the pediatric burn population.

Background discuss the history of fluid resuscitation, current resusci-

Burn injury is a leading cause of unintentional death and tation practices, and future directions of resuscitation
injury in children until 14 years of age (as high as the for the pediatric burn population.
third most common cause in children ages 5 to 9) [1, 2].
While many of these injuries are minor and can be Review
treated as outpatients, approximately 5% are considered History of fluid resuscitation
moderate to severe injuries and require hospitalization Fluid resuscitation as a treatment for burn injury is
[3]. It is generally believed that burns larger than 15% thought to date back to the eighteenth century when
total body surface area (TBSA) lead to the initiation of Gerard van Swieten administered fluid via enema to re-
the systemic inflammatory response syndrome requiring hydrate burn victims [7]. The idea of fluid resuscitation
IV fluid resuscitation to prevent burn shock and death, in burn patients gained further traction when Ludwig
while smaller burns are able to be treated with oral rehy- von Buhl made the correlation between the fluid losses
dration alone [4]. Prompt resuscitation is critical in in burn patients and in those with cholera and advocated
pediatric patients due to their small circulating blood for the administration of saline solution to replace losses
volumes. Delays in resuscitation, even as short as [8]. Unfortunately, further work investigating the fluid
30 min, due to difficulty with IV access or failure to losses and resuscitation of burn patients was not under-
recognize size or severity of the burn can result in taken until the 1930s when Frank Underhill analyzed the
increased rates of complications such as acute renal fail- composition of the fluid in blisters of burn-injured
ure, increased hospital length of stay, and increased patients and found that it was similar in character to
mortality [5, 6]. The basic principles of resuscitation are plasma [9]. The formulas that were designed for fluid
the same in adults and children; however, children are resuscitation of burn-injured patients in the decade
not simply “little adults”. They have unique physiologic following Uphill’s work utilized plasma and based their
needs that must be adequately addressed to successfully estimates of fluid required on patient weight, and either
care for burn-injured children. In this review, we will total serum protein level or hematocrit [10–12]. The size
of the burn was not a consideration in any of these
* Correspondence: [email protected] formulas.
1
Department of Surgery, University of Iowa Hospitals and Clinics, 200
Hawkins Drive, JCP 1500, Iowa City, IA 52242, USA In November, 1942, Oliver Cope and Francis Moore
Full list of author information is available at the end of the article utilized this knowledge and improved upon it as they
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Romanowski and Palmieri Burns & Trauma (2017) 5:26 Page 2 of 9

treated the victims of the Cocoanut Grove nightclub fire. less than 30% TBSA received 2 ml/kg/%TBSA burn in
Cope and Moore recognized the relationship between the first 24 h, those with 30–60% TBSA received 2.5 ml/
the amount of fluid resuscitation required and the size kg/%TBSA burn in the first 24 h, and those with greater
of the burn. Their formula for IV fluid resuscitation used than 60% TBSA received 3 ml/kg/%TBSA burn of low
equal parts of plasma and saline and prescribed 150 ml molecular weight dextran. Single figure formulae have
of fluid for each 1% TBSA burn plus maintenance fluids become the cornerstone of adult burn fluid resuscitation.
during the first 24 h following injury [13]. Half of this The most frequently used formula in current burn care
fluid is given over the first 8 h, and the second half of is the Parkland formula, developed by Baxter and Shires
the fluid is administered over the next 16 h (see Table 1). following a series of studies on dogs [16, 17]. The Park-
This pattern of fluid administration is replicated in most land formula was a departure from previous formulas
subsequent formulas. This was the advent of formulas because it did not use any colloid. It prescribes 4 ml/kg/
that are classified as “two figure formulae” which %TBSA burn in the 24 h given in the manner described
accounted for burn-related fluid losses separate from es- previously (half given in the first 8 h and the remaining
timations of maintenance fluid needs. The two-figure ap- half in the next 16 h). The Brooke formula was also
proach provides safeguards for the young, the obese, and modified to a single figure formula with a burn-injured
children with large burns. The two most well known of patient receiving 3 ml/kg/%TBSA burn over 24 h of lac-
the “two figure formulae” are the Evans formula and the tated Ringer’s without the addition of colloid.
Brooke formula. In 1952, the Evans formula was devel-
oped [14]. This formula utilized 2 ml/kg/%TBSA Current pediatric resuscitation practices
burn plus 2000 ml of maintenance fluids to replace nor- The initial resuscitation formulas that were developed for
mal losses. The Evans formula utilized one-half plasma adult burn-injured patients were initially used in burn-
and one-half crystalloid (normal saline). The Brooke for- injured children with “proportionally smaller quantities”
mula was developed in 1953 by Reiss et al. and is similar [18]. This way of thinking was problematic for many rea-
to the Evans formula in that it prescribes 2 ml/kg/ sons. Children have unique fluid needs after burn injury,
%TBSA burn to be administered in the first 24 h [15]. It and the distribution of their body surface area (BSA) is dif-
differs in the amount of plasma that is provided, and the ferent than that of adults. Fluid resuscitation efforts for
crystalloid used is lactated Ringer’s. The Brooke formula children were aided by the work of Lund and Browder
uses one-fourth plasma and three-fourth crystalloid. who created easy-to-use diagrams for estimating burn size
In contrast with two figure formulae, single figure for- that took into account the differences between adults and
mulae do not consider the maintenance needs separate children [19]. Unfortunately, the weight- and burn size-
from the burn resuscitation fluids. They combine all of based formulas that have been developed and used suc-
their fluid needs into a single formula. Gelin was the cessfully in adult patients are problematic for pediatric
first to propose a single figure formula. He proposed burn patients because they have proportionally larger BSA
three levels of fluid resuscitation. Patients with burns to mass ratios than adults which leads to under- or over-

Table 1 Adult formulas for burn fluid resuscitation

Formula Crystalloid Colloid Glucose Instructions for administration
Cope 75 ml/%TBSA burn oral electrolyte 75 ml/%TBSA burn FFP 2000 ml fruit juice PO Half over the first 8 h, half over the
and replacement solution or 2000 ml 5% dextrose IV second 16 h
Moore
Evans 1 ml/kg/%TBSA burn of NS 1 ml/kg/%TBSA burn FFP 2000 ml 5% dextrose Half over the first 8 h, half over the
second 16 h
Brooke 1.5 ml/kg/%TBSA burn of LR 0.5 ml/kg/%TBSA burn FFP 2000 ml 5% dextrose Half over first 8 h, half over second
16 h
Gelin None <30% TBSA burn: 2 ml/kg/%TBSA burn None Half over the first 8 h, half the over
of low molecular weight dextran second 16 h
30–60%TBSA: 2.5 ml/kg/%TBSA burn
of low molecular weight dextran
>60% 3 ml/kg/%TBSA burn of low
molecular weight dextran
Parkland 4 ml/kg/%TBSA burn of LR None None Half over the first 8 h, half over the
second 16 h
Revised 3 ml/kg/%TBSA burn of LR None None Half over the first 8 h, half over the
Brooke second 16 h
%TBSA percent total body surface area, NS normal saline, LR lactated Ringer’s, FFP fresh frozen plasma
Romanowski and Palmieri Burns & Trauma (2017) 5:26 Page 3 of 9

resuscitation depending on the clinical situation. In gen- Formula and the Galveston Formula. Shriners Hospitals
eral, it has been found that the standard formulae under- for Children in Cincinnati developed their own formula
estimate the fluids needed. It has been suggested that which is similar to the Parkland formula but adds in a
pediatric patients require approximately 6 ml/kg/%TBSA maintenance fluid calculation based on BSA [26]. In older
burn [20, 21]. Recognition of this problem has led to the children, they provided lactated Ringer’s at 4 ml/kg/
development of pediatric-specific formulas. %TBSA burn + 1500 ml/m2 total BSA (1/2 of total volume
The principles of fluid resuscitation are similar for over 8 h, rest of the total volume during the following
children and adults, but there are specific differences as 16 h). In younger children, their formula for resuscitation
well. In general, Ringer’s lactate solution should be was much more complex. Younger children received the
started in patients of all age groups. Due to their limited same 4 ml/kg/%TBSA burn + 1500 ml/m2 total BSA over
glycogen stores, infants are at risk of hypoglycemia if a the first 24 h, but the composition of the fluid changed
glucose source is not provided as part of their resuscita- every 8 h. In the first 8 h, the fluid was lactated Ringer’s
tion. Their blood glucose levels should be monitored with 50 mEq of sodium bicarbonate. The second 8 h was
closely, and a source of 5% dextrose is provided as well. lactated Ringer’s alone, and the third 8 h was lactated
As stated earlier, the volume of fluid required per per- Ringer’s plus 12.5 g of 25% albumin per liter. The team at
cent burn is higher in children due to their increased Shriners Hospitals for Children in Galveston developed a
baseline BSA. Therefore, pediatric burn resuscitation formula that uses only BSA [27]. The Galveston formula
formulas are always two figure formulae that calculate provides 5000 ml/m2 BSA burn as a resuscitation fluid
an estimated fluid resuscitation (EFR) and add mainten- and 2000 ml/m2 total BSA as a maintenance fluid. As with
ance fluids (MFs) with or without dextrose depending the previously described adult formulas, half is given over
on the child’s age and size. The cutoff for using adult the first 8 h and the remainder is given over the next 16 h.
formulae depends on the source, but it is generally felt The fluid utilized in this formula is lactated Ringer’s solu-
to be somewhere between 30 and 50 kg. tion with 12.5 g of 25% albumin per liter plus 5% dextrose
Kyle and Wallace described one of the first formulas as needed.
specifically for children [22]. Their method was based on There has not been a head-to-head comparison of
%TBSA burn, depth of injury, and determination of nor- the two commonly used pediatric formulas. One
mal blood volume, as well as normal metabolic require- group has attempted to model the use of the two dif-
ments for age and weight. The first formula that moved ferent formulas over a range of patient weights and
beyond using only patient weight was developed by Eagle burn sizes and compare these to the physiologic
in 1956 [23]. This formula uses 30 ml/%TBSA burn plus norms of children, but has not examined the use of
10% of body weight in kilograms and 4000 ml/m2 BSA in the formulas in actual practice [28]. They found that
the 48 h following injury (see Table 2). The fluid used in while the Cincinnati formula predicted all physiologic
this formula is 5% dextrose and 0.66 normal saline with losses, the Galveston formula was more practical as a
20 g of albumin per liter. Several other formulae were de- guideline since it allowed for more physiologic vari-
veloped over the next decade that used %TBSA burn, pa- ability in their models. Beyond simply which is the
tient weight, and patient BSA to determine the initial fluid “better” formula, there has also not been a study in
requirements [24, 25]. pediatric patients that looks at predicted versus actual
In the current practice, there are two main formulas fluids given. This is a much needed area of study as
that are utilized in pediatric burn patients: the Cincinnati both over- and under-resuscitation is problematic.

Table 2 Pediatric formulas for burn fluid resuscitation

Formula Crystalloid Colloid Glucose Instructions for administration
Eagle 30 ml/%TBSA burn + 10% 20 g of albumin per liter 5% dextrose Administered over 48 h
weight (kg) + 4000 ml/m2
BSA of 0.66 normal saline
Cincinnati 4 ml/kg/%TBSA burn + 12.5 g of 25% albumin per liter 5% dextrose Half over the first 8 h, half over the next 16 h
(younger children) 1500 ml/m2 total BSA of LR of crystalloid in the last 8 h of as needed Composition of fluid changes every 8 h
first 24 h First 8 h 50 meq/l of sodium bicarbonate
was added. Second 8 h was LR alone. Third
8 h adds albumin
Cincinnati 4 ml/kg/%TBSA burn + None 5% dextrose Half over the first 8 h, half over the next 16 h
(older children) 1500 ml/m2 total BSA of LR as needed
Galveston 5000 ml/m2 BSA burn + 2000 ml/ 12.5 g of 25% albumin per 5% dextrose Half over the first 8 h, half over the next 16 h
m2 total BSA of LR liter of crystalloid as needed
%TBSA percent total body surface area, BSA body surface area, LR lactated Ringer’s
Romanowski and Palmieri Burns & Trauma (2017) 5:26 Page 4 of 9

Endpoints of resuscitation example, abnormal admission arterial lactate levels and

While a lot of research has gone into the creation of re- base excess values correlate with the magnitude of injury
suscitation formulas, it is critical to remember that they and are now recognized as markers of global poor perfu-
are merely estimates of the amount of fluid that will be sion and uncompensated shock [41]. Failure of these
required for a given burn-injured patient. Resuscitation values to correct over time predicts mortality [42–44].
formulas should be used to initiate therapy. However, There are, however, no prospective studies to support the
the IV fluid resuscitation rate should be reevaluated on use of lactate clearance to guide fluid resuscitation in adult
an hourly basis and IV rate adjusted accordingly. Both or pediatric burn patients. Additionally, measures such as
over-and under-resuscitation are equally problematic in ScvO2 that have shown promise in guiding early goal di-
pediatric burn-injured patients. Under-resuscitation leads rected therapy in the septic patient have not been exam-
to burn shock, suboptimal tissue perfusion, end-organ fail- ined or validated in monitoring burn resuscitation [45].
ure, and death [29]. The concept of over-resuscitation or Novel methods of measuring physiologic parameters are
“fluid creep” was described by Dr. Pruitt in 2000 and is being developed and utilized in both pediatric and adult
known to occur when burn patients are over-resuscitated burn patients. In adult patients, standard Parkland resusci-
with excessive amounts of fluid [30]. Despite acknowledg- tation was compared to resuscitation guided by invasive
ing that over-resuscitation is occurring, it has continued thermodilution (TDD) measurements in patients with
to be a problem with the 24-h crystalloid volumes of three greater than 20% TBSA burn [46]. This study found that
recent studies ranged from 4.6 to 6.3 ml/kg/%TBSA patients in the TDD who directed resuscitation received
burn [31]. Over-resuscitation can lead to abdominal com- significantly more fluid during the initial 24 h following
partment syndrome [32], compartment syndrome of the injury, but there were no significant differences in preload
limbs [33], and pulmonary edema leading to tracheostomy or cardiac output parameters between the groups despite
that might not otherwise be necessary [34]. the differences in the amount of fluid they received. In the
In order to ensure that patients are not being either pediatric burn population, minimally invasive transpul-
over- or under-resuscitated, IV fluid rates need to be monary thermodilution (TPTD) has been used to measure
adjusted based on urinary output (UO). Hourly UO hemodynamic parameters in 79 patients with greater
continues to be the most commonly used endpoint in than 40% TBSA burn [47]. They found that in these
guiding the administration of resuscitation fluids [35]. In patients, the hyperdynamic circulation that is classic-
children weighing less than 30 kg, the UO goal is 1 ml/ ally found in burn patients begins within the first
kg/h. In children over 30 kg, a UO of 0.5 ml/kg/h is the week of hospitalization and continues through their
goal. Urine volumes less than or greater than this re- entire ICU course. They did not attempt in this study
quire adjustment in fluid resuscitation rates. Despite our to guide resuscitation using the hemodynamic param-
reliance on this measure, the optimal hourly UO goal eters that they obtained. This is another area of pos-
has never been accurately defined. “Permissive oliguria” sible study for the use of TPTD in pediatric patients.
has even been suggested as an appropriate approach Due to the fact that cardiac output decreases during the
[36]. Despite a focus on urine output as an endpoint, it first 24 to 36 h after major burn injury, children with
is not the only factor in determining adequacy of resus- burns greater than 40% TBSA should have advanced
citation. As a resuscitation endpoint, UO is practical and monitoring including central venous pressures so that
works well in many cases, but it is far from perfect. The their response to fluids can be adequately assessed. Chil-
correlation between UO and measures of oxygen deliv- dren receiving IV fluid rates twice that were predicted by
ery or tissue perfusion is not strong [37]. In fact, in prac- the Parkland formula, with continued inadequate urine
titioners who do not have a lot experience, UO may be output, are likely to have either heart failure or other
prone to misinterpretation especially in the presence of complications of over-resuscitation, including abdominal
IAH or ACS where oliguria may be due to diminished compartment syndrome or pleural effusion [48].
renal perfusion rather than hypovolemia [38, 39]. Sheridan In general, the treatment for hypotension in pediatric
et al. suggest that in infants, the endpoints of resuscitation burn-injured patients is fluid resuscitation. However,
include sensorium (lightly asleep but arouses to tactile even proper fluid resuscitation of burn shock may not
stimuli), physical examination (clear breath sounds and achieve complete normalization of physiologic variables
warm distal extremities), pulse (120–180 beats per mi- due to the fact that burn injury leads to continued
nute), systolic blood pressure (60–80 mmHg), and urine cellular and hormonal changes in the patient [4]. In
output (1–2 ml/kg/h) [40]. these cases, the use of vasopressors may be warranted.
In modern burn units, there are far more sophisticated One study in adults suggests that dobutamine may be a
methods to measure response to burn resuscitation than pressor of choice for burn patients as it increases the
UO. Many of these monitoring tools are able to assess the cardiac index which is shown to be low in patients who
moment-to-moment physiological state of the patient. For have poor outcomes [49]. Other studies suggest the use
Romanowski and Palmieri Burns & Trauma (2017) 5:26 Page 5 of 9

of norepinephrine for burn shock refractory to fluid re- randomized control studies required to fully delineate
suscitation [50]. To date, there are no papers specifically the effects of colloid have not yet been conducted.
on the use of pressors in the resuscitation of pediatric
burn patients. While it is known that pressors are re- Artificial colloids
quired in some burn patients, their role and choice of There was initially a lot of interest in artificial colloids
vasopressor remains an area in need of investigation. (hydroxyethyl starch (HES) and dextrans) as possible
colloids to use as adjuncts to burn resuscitation in order
Areas of controversy and future directions to limit the amount of crystalloid that is given and
Colloid prevent over-resuscitation and its complications. In
The use of colloids in burn resuscitation is an area particular, HES has been studied as an adjunct to fluid
where considerable controversy exists. Plasma proteins resuscitation, although none of these studies have been
are important in maintaining oncotic pressure to balance done in a pediatric burn population. A randomized
the outward hydrostatic pressure. The need to adminis- study of 26 patients was done comparing a pure crystal-
ter large volumes of crystalloid fluids during burn resus- loid resuscitation to one that substituted one third of the
citation to prevent burn shock leads to a decrease in crystalloid volume with 6% HES [57]. They found that
plasma protein concentration and worsens extravascular patients receiving HES required less overall fluid in the
egress of fluid and edema formation. Replacing plasma first 24 h following injury and lower C-reactive protein
proteins using colloids (albumin, plasma, dextran, and levels. However, when 10% HES was used in burn resus-
hydroxyethyl starch) could in theory mitigate this effect. citation, there was a trend toward increased renal failure
It was this theory that led to the use of colloids in the and increased mortality although these did not reach the
early burn resuscitation formulas such as those devel- level of significance [58]. Despite the mixed evidence for
oped by Cope and Moore [13] and Evans et al. [14]. the use of artificial colloids in burn resuscitation, the risk
These early formulas utilized fresh frozen plasma (FFP), of impaired hemostasis, impaired renal function, and
but unfortunately, this is problematic as blood products increased risk of death that was found in the use of
carry with them a risk of blood-borne infectious trans- these fluids in other critically ill populations has all but
mission and is a known risk factor for development of eliminated their use in the burn population [59, 60].
acute lung injury (TRALI) [51]. Due to these concerns Given that pruritus is already a problem for burn
and the fact that FFP is a limited resource, its use has patients, an additional concern was the severe and pro-
largely been reserved to treat patient with active bleed- longed pruritus that is caused by the deposition of
ing or coagulopathy. hetastarch in the skin [61].
The use of colloid at all in initial burn resuscitation
was called into question by radioisotope studies con- Albumin
ducted by Baxter and Shires [16] and Pruitt et al. [52] The large-scale studies needed to determine the efficacy
that demonstrated that in the early phases of resuscita- and potential pitfalls of using albumin in children have
tion (first 24 h after injury), plasma expansion was inde- also not been conducted at this time, but there are a few
pendent of the type of fluid given because the capillary smaller studies that suggest that albumin might be bene-
integrity is not sufficient enough to allow for colloid to ficial in pediatric burn patients. Faraklas et al. [62] retro-
influence the intravascular oncotic pressure. In fact, it spectively reviewed their resuscitation protocol which
has been demonstrated that early administration of utilized albumin as a rescue therapy. When patients
colloid increases pulmonary edema. It has been demon- were well above their calculated Parkland resuscitation
strated that the rate of edema formation is highest or were beginning to show signs of complications related
between 8 and 12 h following burn injury [53, 54]. Non- to edema, 1/3 of their fluid requirements were switched
burned tissues experience a transient loss in capillary in- to 5% albumin. In order to measure the success of their
tegrity and ability to sieve plasma proteins which is resuscitation, they looked at the ratio of intake to output
quickly regained. Because of this, almost all studies that (I/O ratio). As patients required more fluid, their I/O ra-
have looked at the use of colloids in burn resuscitation tio escalated. This ratio corrected back to the baseline
have found reduced edema in unburned tissue but no levels with the addition of albumin in the study without
change in the edema in the burn itself [55, 56]. The tran- any obvious complications of its administration. The use
sient nature of the capillary leak has prompted some to of albumin early (within 8–12 h of burn injury) has also
adopt an approach where they start colloid administra- been examined in children with burns larger than 15%
tion during the second half of the first 24 h following TBSA [63]. This study found that children who received
burn injury. While there is evidence that indicates that albumin early required lower crystalloid fluid volumes
adding colloid to burn resuscitation formulas can and had fewer fluid volume-related complications. Un-
decrease volume requirements, the large multicenter fortunately, this was a very small study with only 23
Romanowski and Palmieri Burns & Trauma (2017) 5:26 Page 6 of 9

patients in each group. As in adults, more research is solutions to correct hypovolemia and to restore periph-
needed in the pediatric population to determine what eral perfusion. This post-burn volume replacement in-
role albumin should play in burn resuscitation and when creases oxygen delivery to previously ischemic tissue,
the ideal time for its administration is. leading to ischemia-related tissue injury and the produc-
tion of oxygen free radicals. Due to its antioxidant prop-
Hypertonic saline erties, there has been a significant amount of interest in
Hypertonic saline has been suggested as a burn resuscita- the use of high-dose vitamin C in burn resuscitation to
tion fluid because it helps to correct the extracellular so- ameliorate the effects of hypovolemic and ischemic tis-
dium deficit which is an important component of burn sue damage. High-dose vitamin C is thought to protect
shock [64]. Hyperosmolarity helps expand plasma volume against membrane lipid peroxidation to limit capillary
by shifting water into the intravascular space. The hyper- leak and is a potent oxygen-derived free radical scaven-
osmolar load may also cause an osmotic diuresis which ger [71]. Matsuda et al. [72, 73] have conducted a num-
improves early urine output preventing over-resuscitation ber of studies in a guinea pig burn model which found
and the associated complications. The price of this shift is that burn resuscitation with lactated Ringer’s combined
intracellular water depletion, but it is as yet unclear with a vitamin C infusion led to reductions in the
whether this intracellular water depletion is harmful to pa- hematocrit, increased CO, decrease wound edema, and
tients. Studies from the 1970s to 1980s by Monafo [65] decreased fluid resuscitation volume compared with the
and Moylan et al. [66] found that patients treated with use of lactated Ringer’s alone. These effects were seen
hypertonic lactated saline required smaller fluid volumes irrespective of the depth of the wound and even when
to maintain adequate urine output when compared to pa- initiation of treatment was delayed by as much as 6 h
tients treated with isotonic crystalloids. Oda et al. [67] post-burn injury [74]. In a 40% TBSA burn sheep model,
demonstrated that the reduction in fluid volume was clin- vitamin C started within an hour of burn injury, reduced
ically significant as patients who received hypertonic saline fluid requirements by 30% at 6 h and by 50% at the 48-h
had lower intra-abdominal pressures. Large-volume post-burn injury time point when compared to trad-
hypertonic saline can increase plasma sodium levels to itional resuscitation with lactated Ringer’s [75].
160 mEq/L; when this level of hypernatremia occurs, there There have been two prospective human trials evaluat-
is a decrease in urine output below 50 ml/h [68]. This ing the use of high-dose vitamin C in burn resuscitation
level of hypernatremia is cautioned against. Therefore, in of adults. Mann et al. [76] conducted a blinded random-
using hypertonic saline as a resuscitation fluid, it is essen- ized control trial in adults with burns ≥30% TBSA that
tial to monitor serum sodium levels frequently as severe compared vitamin C at 1 g/h to normal saline which
hypernatremia can lead to acute renal failure. In fact, the found no significant differences in net fluid intake at 24,
largest study looking at hypertonic saline was a retrospect- 48, or 72 h. In an unblinded study where patients were
ive study using historical controls which found that pa- randomized by month of admission, Tanaka et al. [77]
tients who received hypertonic saline had a fourfold compared resuscitation using 66 mg/kg/h ascorbic acid
increase in acute renal failure (40% vs 10.1%, p < 0.001) and lactated Ringer’s to standard resuscitation with lac-
and had twice the mortality rate (53.8% vs 26.6%, p < tated Ringer’s alone. They found that high-dose vitamin
0.001) as their counterparts who received standard crystal- C significantly reduced 24-h resuscitation fluid volumes
loid resuscitation [69]. Despite the theoretical benefits and (45% decrease, 5.5 ml/kg vs 2.1 ml/kg) and weight gain
some successful trials using hypertonic lactated saline, compared with controls. Additionally, there were a de-
there has been decreased enthusiasm for the use of hyper- creased number of ventilator days in the treatment
tonic saline especially given the more recent data that sug- group as well. In addition to these prospective studies,
gests that there is an increased risk of acute kidney injury there have been numerous retrospective studies that
(AKI) following the administration of chloride-containing have used an infusion of 66 mg/kg/h of high-dose vita-
solutions in the critically ill [70]. While hypertonic saline min C as an adjunct to crystalloid resuscitation. These
has been used in studies of children with traumatic brain studies have found that high-dose vitamin C reduces the
injuries, there have been no large studies looking at the volume of fluid needed for resuscitation. In particular,
use of hypertonic saline in the resuscitation of pediatric they have found that addition of high-dose vitamin C
burn patients. Further research on the potential risks and keeps total resuscitation close to the Parkland predic-
benefits of hypertonic saline in the pediatric burn popula- tion of 4 ml/kg/%TBSA burn which is up to a 30%
tion must be undertaken. reduction from the predicted volumes required [78,
79].
High-dose vitamin C (ascorbic acid) While the initial data on high-dose vitamin C infusions
As has already been discussed, the treatment of major seems positive in its ability to reduce fluid resuscitation
burn injury includes the administration of crystalloid volumes and subsequent edema, there are a number of
Romanowski and Palmieri Burns & Trauma (2017) 5:26 Page 7 of 9

concerns associated with its use that have become ap- ≥20% TBSA resulted in significant reductions in total
parent. One concern is the osmotic diuresis that occurs crystalloid resuscitation volumes (over the first 48 h)
due to high-dose vitamin C. The fear is that patients and UO within the target range significantly more than
may become dehydrated if fluids are titrated down too their historical controls [83]. This ultimately led to shorter
aggressively in light of this diuresis elevating UO values. durations of mechanical ventilation, decreased ICU length
There is some data to support this concern. When of stay, and improved rates of survival. Kulkarni et al. [36]
treated with high-dose vitamin C, there is an increase in conducted a similar study that utilized a computerized de-
UO despite a significant decrease in fluid volume [50, cision support tool based on an Excel spreadsheet with a
51]. Additionally, high-dose vitamin C did not seem to series of “if–then” logical statements. The computer sup-
have an effect on markers of resuscitation other than port group patients required fewer escharotomies and no
UO, such as vasopressor requirements or base deficit. episodes of abdominal compartment syndrome. Patients
Due to concerns about safety and unclear efficacy, there in the computer support group did experience 1 to 2 h pe-
have yet to be studies using high-dose vitamin C as an riods of anuria, between 6 and 10 h post-burn that did not
adjunct to resuscitation in the pediatric population, al- occur in the control patients. This did not however result
though anecdotally there are some centers that use it in in episodes of early renal failure. While the use of comput-
children. There has, however, been a small study in chil- erized resuscitation protocols is promising, there have not
dren looking at the effects of oral supplementation of been any large-scale multicenter studies, and it has yet to
vitamin C, vitamin E, and zinc on wound healing. They be tested in a pediatric burn population. Computer-aided
found that when vitamin C is given at 1.5 times the resuscitation protocols could be especially helpful in chil-
upper intake limit, wounds healed faster than in the un- dren as they are particularly sensitive to over- and under-
treated group [80]. The use of high-dose vitamin C in resuscitation.
the pediatric burn population is another area that needs
further study to determine if the beneficial effects seen Conclusions
apply to children or if the risks seen in adults outweigh Resuscitation of burned children has improved markedly
the benefits. over the years. Adequate fluid resuscitation is essential to
optimizing the survival of burned children. Although
Computer-aided resuscitation protocols multiple regimens and fluids are available for resuscitation,
In burn resuscitation, it is important to remember that alteration of fluid infusion rate guided by clinical endpoints
one is always dealing with a shock state and are often is the mainstay of therapy. In the future, closed-loop resus-
walking the line between class II and class III shock. The citation methods may improve pediatric burn outcomes.
practitioner’s level of discomfort with a patient in the
shock state and our desire to eliminate it as quickly as Acknowledgements
possible often leads to over-resuscitation and its associ- None
ated complications. In an effort to deal with practitioner
discomfort and standardize resuscitation as much as Funding
The authors received no funding for this work.
possible, computerized systems have been developed.
Closed-loop resuscitation is a fully automated system
Availability of data and materials
that leads to continuous adjustment of the fluid infusion Not applicable.
rate based on a computer-controlled algorithm. The de-
vice adjusts the infusion rate to achieve a defined physio- Authors’ contributions
logical endpoint (in most cases, this is UO). A study by KSR and TLP did the writing and editing of the manuscript and concept of
the study. Both authors read and approved the final manuscript.
Hoskins et al. [81] compared technician-guided resuscita-
tion with the closed-loop system. The closed-loop system
Ethics approval and consent to participate
resulted in significantly less variation in fluid infusion Not applicable.
rates and UO, a significantly lower incidence of UO being
under target range, and a trend toward lower total fluid Consent for publication
volumes for resuscitation in the first 24 h. All authors give consent for publication; no patient data presented.
Most physicians are not comfortable with a completely
closed-loop system. This led to the development of the Competing interests
The authors declare that they have no competing interests.
Computerized Decision Support System (CDSS) [82].
This system provides recommendations for fluid resusci- Author details
1
tation to the clinician on an hourly basis, and then, the Department of Surgery, University of Iowa Hospitals and Clinics, 200
Hawkins Drive, JCP 1500, Iowa City, IA 52242, USA. 2Shriners Hospitals for
clinician is free to accept or reject those recommenda- Children Northern California, Sacramento, California, USA. 3University of
tions. Using this system in adult patients with burns California Davis, Davis, California, USA.
Romanowski and Palmieri Burns & Trauma (2017) 5:26 Page 8 of 9

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