Burns Open 7 (2023) 51–58

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Burns Open
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Initial fluid resuscitation guided by the Parkland formula leads to high fluid
volumes in the first 72 h, increasing mortality and the risk for kidney injury
Laura Lindahl a, *, Tuomas Oksanen a, Andrew Lindford b, Tero Varpula a
a
Division of Intensive Care, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
b
Department of Plastic Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Our Burn center has used the Parkland formula (4 ml/kg/TBSA%) adjusted by physiological pa­
Fluid resuscitation rameters to guide fluid resuscitation in burn patients. Our main objective was to examine fluid resuscitation in
Parkland formula patients with major burn injury and its effect on mortality, need for renal replacement therapy (RRT) and the
Over resuscitation
length of stay (LOS) in the Intensive Care Unit (ICU). Further aims were to determine which factors were
Acute kidney injury
Burn resuscitation protocol
associated with fluid resuscitation volumes during the first 24 h, and whether these fluid volumes had an as­
sociation with the volumes infused during the next 48 h.
Methods: This retrospective observational study accrued patients (N = 46) admitted to the Helsinki Burn Center
between 2016 and 2018 with burn injuries ≥ 20% TBSA. The national intensive care registry and the electronic
patient record system provided data on fluid infusions, urine output, laboratory measurements, presence of
inhalation injury, surgical procedures within 72 h from injury, patient demographics, need for renal replacement
therapy and mortality. Patients were divided into groups based on infused fluid volumes and univariate re­
gressions were performed to identify factors associated with fluid volumes.
Results: 48% of the patients received fluids more than 6 ml/kg/TBSA% during the first 24 h. 35% of the patients
received fluid volumes exceeding the Ivy index (250 ml/kg/d) and was associated with higher TBSA%, SOFA and
SAPS scores as well as increased mortality and need for RRT. Higher lactate and lower base excess were asso­
ciated with higher fluid volumes. Urine output had no association with the resuscitation volumes. Larger
resuscitation volumes during the first 24 h were associated with larger fluid volumes given also during the next
48 h. Higher cumulative fluid volume in 0–72 h resulted in increased need of RRT and higher ICU mortality.
Conclusion: Using the Parkland formula and adjusting the infusion based on physiological parameters leads to
over resuscitation in many of the patients. It seems that the more fluids are given during the initial resuscitation
phase, the more fluids are also administered during the subsequent phase. Higher cumulative fluid volumes are
associated with RRT requirements and higher mortality. We postulate that starting fluid resuscitation with a
lower infusion rate could be beneficial, as it may lead to smaller cumulative fluid volumes during the first 72 h,
leading to reduced mortality and kidney injury.

1. Introduction
A severe burn injury, usually classified as a burn injury over 20%
total body surface area (TBSA), results in a systemic inflammatory
response. This causes increased capillary permeability which develops
within 1–6 h from the injury and reaches a maximum at 12–24 h [1].
Without fluid therapy, systemic capillary leak leads to intravascular
hypovolemia and hypovolemic shock. Increased capillary permeability
results in fluid accumulation in the extravascular space and tissue
swelling which in turn impairs tissue oxygenation as the distance

Abbreviations: RRT, Renal replacement therapy; LOS, Length of stay; ICU, Intensive care unit; SOFA score, Sequential Organ Failure Assessment score; SAPS,
Simplified Acute Physiology Score; TBSA, Total Body Surface Area; AKI, Acute Kidney Injury; CI, Cardiac Index; SVV, Stroke Volume Variation; CRT, Capillary Refill
Time; Hb, Haemoglobin; BE, Base Excess; APACHE score, Acute Physiology and Chronic Health Evaluation score; CCI, Charlson Comorbidity Index; KDIGO, Kidney
Disease Improving Global Outcomes; IQR, Interquartile Range.
* Corresponding author at: Intensive Care and Burn Unit U2, Jorvi Hospital, PL 800, 00029 HUS, Finland.
E-mail addresses: laura.lindahl@hus.fi (L. Lindahl), tuomas.oksanen@hus.fi (T. Oksanen), andrew.lindford@hus.fi (A. Lindford), tero.varpula@hus.fi
(T. Varpula).

https://doi.org/10.1016/j.burnso.2023.03.006
Received 24 March 2023; Accepted 27 March 2023
Available online 1 April 2023
2468-9122/© 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
L. Lindahl et al.
between red blood cells and tissue cells increases. The inflammatory
response associated with a severe burn injury can also lead to temporary
cardiac dysfunction. All these factors contribute to impaired delivery of
oxygen at the cellular level in the acute phase of burn injury [2,3].
Fluid resuscitation has a key role in the acute treatment of major
burns. The Parkland formula for primary burn resuscitation was pub­
lished by Charles Baxter in 1968 [4]. Since then, it has been the main
formula for guiding fluid resuscitation in burn patients. Several other
formulas, including modifications of the Parkland formula, to predict
fluid requirements have been proposed and adopted for clinical use [5].
Most of them implement body weight and TBSA. Some formulas propose
the use of colloid infusion from the start of the fluid resuscitation aiming
to reduce the total fluid volume. Different formulas give significantly
different predictions of the required resuscitation volumes, which affect
the execution of the fluid resuscitation and the actual fluid volumes
given to the patient during the resuscitation phase. A quantitative re­
view by Shah et al in 2020 suggests that majority of burn patients
receive larger volumes than predicted by the Parkland formula with
great patient to patient variability [6], whereas Baxter reported that
only 12% of the patients would require more than 4.3 ml/kg/h [7].
There is growing evidence that excessive fluid administration in­
creases mortality and development of acute kidney injury (AKI) in
critically ill patients [8–14]. In the context of burn injury, the term “fluid
creep” has been used when the administered fluid volume exceeds the
resuscitation volume predicted by the Parkland formula [15,16].
Another concept to describe excessive fluid administration is the so-
called Ivy index. It is defined as 250 ml/kg given during the first 24 h
after injury. Exceeding the Ivy index has been reported to be associated
with an increased risk for abdominal compartment syndrome which is a
risk factor for AKI, and death. [17,18] On the other hand, one of the
pathophysiological mechanisms for early AKI after burn is thought to be
hypovolemia, together with increased inflammatory mediators and
cardiac dysfunction [19].
Chung et al compared burn patients resuscitated by the modified
Brooke formula (2 ml/kg/TBSA%/24 h) and the Parkland formula (4
ml/kg/TBSA%/24 h). They found that the Parkland group received
more fluid in the first 24 h. There were no significant differences in
complications or mortality between the groups but exceeding the Ivy
Index (250 ml/kg) was an independent predictor of mortality and the
Ivy index was more likely to be exceeded in the Parkland formula group.
They concluded that “fluid begets more fluid,” indicating that a higher
initial fluid resuscitation rate results in larger total fluid volumes in 24 h.
[20] It might at least be partly explained by endothelial damage due to
large fluid infusions. A rodent model has shown that systemic glycocalyx
degradation increases with the burn size, resulting in capillary leak and
coagulopathy [21]. A study by Tapking et al. has shown a significant
correlation between the cumulative administered fluid volume over
time and syndecan levels, which act as a proxy to glycocalyx degrada­
tion [22]. This phenomenon has also been seen in septic patients
[23,24]. A small study published in 2013 suggests that a higher resus­
citation volume in the first 24 h correlates with higher volume also in the
second 24 h [25]. To our knowledge, there are only few studies reporting
infused fluid volume beyond the first 48 h in burn patients.
Some studies implicate that goal-directed resuscitation strategies
using arterial waveform analysis may result in lower resuscitation vol­
umes than formula-based resuscitation without an increase in the risk of
AKI or mortality [26,27]. On the contrary, Chiao et al reported in 2018
that aiming for cardiac index (CI) 2.5 l/min/m2 and stroke volume
variation (SVV) less than 12% rather than using normal protocol led to
“unnecessary fluid administration” [28]. There are also other studies
confirming that aiming for normal or supranormal preload parameters
leads to over resuscitation [29–32].
The Parkland formula has been used in clinical practice for the initial
fluid resuscitation in our burn center. Our clinical experience has shown
that the reduction of the fluid infusion rate by half is rarely feasible at
eight hours due to worsening of hemodynamics and other parameters.
52
Burns Open 7 (2023) 51–58
We suspected that the total amount of fluid resuscitation exceeds the
Parkland formula in many cases, increasing the risk of fluid creep. We
also suspected that the fluid resuscitation volume of the first 24 h affects
the volume patients receive during the subsequent days.
Our objective was to examine the current practice of fluid resusci­
tation in patients with major (≥20% TBSA%) burn injury and its effect
on mortality, need for renal replacement therapy (RRT) and the length
of Intensive Care Unit (ICU) stay (LOS) in our burn center. In addition,
we wanted to clarify other factors contributing to increased mortality
and the need for RRT. We also aimed to determine which factors were
associated with the fluid resuscitation volume during the first 24 h, and
whether the volume infused in the first 24 h had an association with the
fluid volumes infused during the next 48 h.
2. Material and methods
2.1. Study design and setting
This is a retrospective study conducted in the Helsinki Burn Center
which serves as Finland’s National Burn center in the Helsinki Univer­
sity Hospital and covers a population of 5.5 million. It is an 8-bed mixed
ICU with an intensivist on site 24/7. Beds are allocated to critical burn
patients as needed. This study was conducted with the consent of the
related departments and approved by the local ethics committee.
Consecutive patients admitted to the intensive care unit between
January 2016 and December 2018 were screened. The inclusion criteria
to the study were: 1) burn injury over 20% TBSA, 2) admission to the
burn center within 12 h of the injury, 3) age ≥ 18 years. The exclusion
criteria were: 1) withdrawal of futile intensive care within 72 h, 2) the
need of intensive care less than 24 h because of less severe injury and 3)
readmission. Data of 46 patients were entered to the study (Fig. 1).
2.2. Monitoring and fluid resuscitation protocol
Routine hemodynamic monitoring included arterial and central
venous lines and monitoring of hourly urine output. Capillary refill time
(CRT) and the clinical assessment of the temperature of peripheral limbs
were used to monitor the microcirculation. Blood gas analyses, lactate,
and haemoglobin (Hb) measurements were performed every two hours
during the first 24 h and less often after that.
The fluid resuscitation protocol during the study period was based on
the Parkland formula. The total predicted fluid volume for the first 24 h
was calculated using 4 ml/kg/TBSA%. Fluid resuscitation was
commenced with the predicted infusion rate using Ringer’s acetate,
which was titrated up or down to achieve the resuscitation targets. The
resuscitation targets were 1) urine output 0.5–1.0 ml/kg/h, 2) main­
taining or improving hemodynamic parameters and 3) slow correction
of laboratory parameters such as lactate, base excess (BE) and Hb to­
wards normal values. Titration of the infusion rate was guided by clin­
ical judgement based on the resuscitation targets and measured
parameters. Our burn center does not use synthetic colloids in burns
resuscitation. Albumin solutions are not included in our protocol, as
there is no strong evidence for albumin decreasing the resuscitation fluid
volumes nor does it reduce mortality [33,34].
ICU discharge criteria in our unit consist of: 1) stable vital organ
functions, and 2) ward nursing resources adequate for the treatment of
the patient.
2.3. Data collection
Data including patient age, sex, length of stay (LOS) in the ICU and
hospital, SOFA [35], APACHE II [36] and SAPS II [37] scores for the first
24 h, ICU mortality and mortality up to 12 months was collected from
the national intensive care registry Intensium (Finnish Intensive Care
Consortium (FICC) database, maintained by Tieto Ltd (Helsinki,
Finland)). ICU mortality was preferred over 28-day mortality because
L. Lindahl et al.
69 readmissions
802 other than burn patients
95 patients with <20%TBSA
burns
5 patients: <18years
15 patients: admitted >12h
after burn accident
12 patients: withdrawal of
intensive care in a hopeless
situation within 72h of
admission in
2 patients: LOS ICU <24h
Fig. 1. Flow diagram showing all excluded patients, resulting in the study population of 46 patients.
ICU LOS was over 28 days in several patients and there were only two
deaths following ICU discharge in the period up to 12 months. Addi­
tional data were retrieved from the local electronic patient record sys­
tems Clinisoft (Centricity Critical Care, GE Healthcare, USA) and Uranus
(CGI Finland Oy, Helsinki, Finland). These data included infused fluid
volumes, urine output, laboratory results (lactate, base excess, haemo­
globin), Charlson Comorbidity Index (CCI) [38] and performed surgical
procedures (escharotomy, fasciotomy, burn excision, tracheostomy) up
to 72 h after admission. AKI was defined with KDIGO criteria [39],
either based on creatinine elevation from baseline or diuresis rate. The
need for RRT during the intensive care period was also registered.
2.4. Data analysis and statistical methods
The data were analysed after dividing the patients into two groups
based on received fluid volume in the first 24 h. A cut-off of 6 ml/kg/
TBSA% was chosen, as we deemed that exceeding the fluid volume
(calculated by the formula) by 50 % would probably be significant.
Another reason to choose this cut-off value was based on the results of
some previous studies, where it was found that using the Parkland for­
mula resulted in median fluid infusion rates of approximately 6 ml/kg/h
[20,40,41]. The patients were also divided into groups based on the Ivy
index in the first 24 h after injury (Ivy index < 250 ml/kg/d and ≥ 250
53
Burns Open 7 (2023) 51–58
All ICU-admissions
n=1046
n=977
Burn ICU-patients
n=175
TBSA%≥20
n=80
Final cohort
n=46
ml/kg/d). The groups were compared in several aspects, including urine
output, requirement for renal replacement therapy, stage of AKI using
KDIGO definition, fluid volumes received during the next 48 h, total
amount of fluids received during the first 3 days of ICU stay, different
laboratory values and mortality. We report categorical variables using
counts and percentages, and continuous variables using medians with
interquartile ranges (IQR) as some of the data were non-normally
distributed.
IBM SPSS Statistics Software 27 was used for the statistical analysis.
The continuous data were compared using Mann-Withney-U test. Cate­
gorical parameters were analysed using Fischer’s exact test because of
small sample size. Univariate logistic regressions were performed to
explain any association between fluid volumes and the need for RRT,
mortality and LOS, and to find the factors associated with fluid resus­
citation volumes in the first 24 h. The results are reported in a table as
odds ratios and 95% confidence intervals. Box-and-whiskers plot was
used to show differences in the total fluid volumes in patients without
the need of RRT and patients receiving RRT, and survivors and non-
survivors.
The results were considered significant when p < 0,05.
L. Lindahl et al. Burns Open 7 (2023) 51–58

3. Results Table 2
Characteristics and outcomes of patients in lower and higher resuscitation rate
A total of 1046 patients were admitted to the ICU during the study groups.
period. After screening for inclusion and exclusion criteria, 46 patients < 6 ml/kg/TBSA% >6ml/kg/TBSA% p
with a severe burn were included in the study (Fig. 1). N = 24 N = 22
The median TBSA% was 32.0% and the median age was 53.7 years. Median (IQR) or N Median (IQR) or N
(%) (%)
Flame injury was by far the most common mechanism of the injury
(84.8%). 22 patients (48%) received fluids over 6 ml/kg/TBSA% during
TBSA% 30.5 (24.3–40.3) 32.5 (29.5–46.4) 0.620
the first 24 h after injury. The median fluid amount administered during
Inhalation injury 3 (12.5%) 8 (36.4%) 0.089
the first 24 h was 5.9 ml/kg/TBSA% in all the patients. Only two patients Hydroxycobalamin 3 (12.5%) 10 (45.5%) 0.021
received fluids less than 4 ml/kg/TBSA%. The overall ICU mortality was Age 54.5 (36.5–67.0) 59.5 (42.0–66.5) 0.723
15.2% and 23.9% of the patients received RRT (Table 1). Male sex 19 (79.2%) 9 (40.9%) 0.015
CCIa 1.0 (0–3.75) 2.0 (1.0–3.0) 0.305
Spont. airway on 15 (62.5%) 11 (50%) 0.552
3.1. Fluid resuscitation during the first 24 h admission
Spont. airway on 3rd day 12 (50%) 4 (18.2%) 0.032
3.1.1. Fluid resuscitation rate KDIGOb > 1 1–3 days 7 (29.2%) 7 (31.8%) 1.000
Data analysis was performed after dividing the patients into two RRTc during ICU stay 4 (16.7%) 7 (31.8%) 0.307
Urine output day 1 (ml/ 0.7 (0.5–1.2) 0.4 (0.4–1.0) 0.524
groups: fluid resuscitation < 6 ml/kg/TBSA% (N = 24) and > 6 ml/kg/
kg/h)
TBSA% (N = 22) during the first 24 h. There was no significant differ­ Creatinine on admission 72 (57–97) 79 (61–96) 0.488
ence between the groups in age, comorbidities, time elapsed between (umol/l)
the injury and admission to ICU, TBSA%, surgical interventions Lowest BEd day 1 − 5.1 (− 8.1–(− 2.9)) − 8.3 (− 12.4– 0.017
(escharotomy, fasciotomy, excision) during the first 3 days, airway on (− 5.2))
Highest lactate day 1 2.1 (1.62–4.0) 3.9 (2.6–6.5) 0.019
admission or frequency of tracheostomies by day 3. Females were
(mmol/l)
overrepresented in the larger fluid volume group. Incidence of inhala­ Hbe max day 1 (g/l) 170 (155–179) 162 (137–183) 0.171
tion injury was not significantly different between the groups. A higher Myoglobin on admission 138 (70–1257) 475 (37–8100) 0.394
number of patients needed mechanical ventilation on day 3 in the larger (ug/l)
Mortality ICUf 2 (8.3%) 5 (22.7%) 0.234
fluid volume group compared to the smaller fluid volume group (81.8%
Mortality hospital 4 (16.7%) 5 (22.7%) 0.718
vs. 50%, p = 0.032). 24 h SOFA, APACHE II and SAPS scores were higher Mortality 12 months 4 (16.7%) 5 (22.7%) 0.718
in the larger volume group. The first and the second day lactate and BE APACHE II 24 h 21.0 (14.0–25.0) 25.5 (19.5–32.3) 0.020
values differed between the groups. None of the patients received blood SAPS 24 h 36.5 (25.5–52.0) 47.0 (35.0–66.0) 0.013
products during the first 24 h. There was no significant difference in SOFA 24 h 6.5 (3.0–8.8) 10.5 (7.0–12.25) 0.001
Baux score 89.8 (73.0–104.0) 94.5 (79.3–101.0) 0.692
mortality and the RRT requirements. ICU length of stay was significantly
ICU length of stay 13.1 (4.1–31.4) 22.9 (16.7–33.8) 0.033
shorter in the smaller fluid group (Table 2). Hospital length of stay 39.5 (28.0–62.0) 45.5 (27.0–62.5) 0.775
Fluids 0–24 h (ml) 14,114 16,631 0.019
(9331–17725) (13871–24249)
Fluids 0–24 h (ml/kg/ 4.69 (4.19–5.21) 7.00 (6.34–8.21) <0.001
TBSA%)
Fluids 0–72 h (ml) 31,713 35,163 0.180
Table 1
(20884–39735) (24370–46364)
Patient characteristics. i
Noradr. max 0–24 h (ug/ 0.07 (0.00–0.24) 0.17–0.21 0.115
Median (IQR) or N (%) kg/min) (0.05–0.29)
Escharotomy within 72 h 14 (58.3) 12 (54.5%) 1.000
Total number of patients 46 Faschiotomy within 72 h 4 (16.7%) 4 (18.2%) 1.000
Age (years) 53.7 (41.8–67.0) Burn operation within 15 (62.5%) 14 (63.6%) 1.000
Male gender (%) 28 (60.9) 72 h
Weight (kg) 80.0 (67.0–90.0)
a
BMIa (kg/m2) 25.8 (23.4–29.2) CCI = Charlson Comorbidity Index.
Charlson Comorbidity Index 1.0 (0.0–3.0) b
KDIGO = KDIGO criteria for acute kidney injury.
Burn TBSA % 32.0 (27.8–42.3) c
RRT = Renal replacement therapy.
Bauxb score 91.5 (75.5–104) d
BE = Base excess.
Inhalation injury 11 (23.9) e
Hb = Haemoglobin.
Time to admission (hours) 3.7 (1.8–6.4) f
APACHEc score (first 24 h) 23.0 (17.0–29.0)
ICU = Intensive care unit.
i
Burn Mechanism (%) Noradr. max = Maximal noradrenalin infusion rate.
Flame 39 (84.8)
Hot fluid 4 (8.7) 3.1.2. Fluid volume
Other 3 (6.5)
Invasive ventilation on the 3rd day 30 (65.2)
The data was also analysed after dividing the patients in groups
Time to excision (days) 2.2 (1.4–3.5) based on the Ivy index (≤250 ml/kg N = 30 and > 250 ml/kg N = 16).
ICUd length of stay (days) 19.3 (8.4–32.2) There were significant differences between the groups with regards to
AKIe within 72 h (KDIGOf 1-3d) 21 (45.7) TBSA%, presence of inhalation injury, APACHE II, SOFA and SAPS
RRTg within 72 h 6 (13.0)
scores. All these were higher in the group that received more fluids.
RRT during ICU stay 11 (23.9)
ICU mortality 7 (15.2) There was no difference in age nor comorbidities. There was also no
a
difference in urine output during the first day in the ICU. There was a
BMI = Body mass index.
b statistically significant difference in favour of the smaller fluid group in
Baux score = Age + TBSA%.
c ICU and hospital mortality, RRT requirements, ICU length of stay and
APACHE = Acute Physiology and Chronic Health Evaluation score.
d
ICU = Intensive Care Unit.
need for mechanical ventilation on day 3 (Table 3).
e
AKI = Acute kidney injury. We did not collect data on intra-abdominal hypertension or
f
KDIGO = Kidney Disease Improving Global Outcomes – criteria for acute abdominal compartment syndrome, but none of the patients underwent
kidney injury. a decompressive laparotomy.
g
RRT = Renal replacement therapy.

54
L. Lindahl et al. Burns Open 7 (2023) 51–58

Table 3 output was within the target range (0.5–1 ml/kg/h) in 22 (47.8%) of the
Characteristics and outcomes in lower and higher fluid volume groups. patients and exceeded the target range in 12 patients (26.0%) Figs. 2a
Fluids ≤ 250 ml/ Fluids > 250 ml/ p and 2b. The rate of noradrenaline infusion was not associated with fluid
kg/d kg/d volumes (Table 4).
N = 30 N = 16 A higher amount of fluid received during the first 24 h of resuscita­
Median (IQR) or N Median (IQR) or N
tion was associated with a higher total fluid volume administered during
(%) (%)
the following 48 h (Fig. 3).
TBSA% 30.0(23.8–32.5) 47.8 (36.3–56.8) <0.001
Inhalation injury 3 (10%) 8 (50%) 0.004
Hydroxycobalamin 5 (16.7%) 8 (50%) 0.036 3.3. Cumulative fluid volume of 0–72 h
Age 57.5 (34.3–72.0) 56,0 (43,3–63,8) 0.460
Male sex 16 (53%) 12 (75%) 0.210
The total amount of fluids infused between 0 and 72 h correlated
CCIa 1 (0–4) 1,0 (0,3–2,0) 0.492
Spont. airway on 22 (73.3 %) 4 (25%) 0.004 with ICU mortality and RRT requirements Fig. 4. ICU LOS was not
admission associated with the fluid volumes.
Spont. airway on day 3 16 (53.3%) 0 (0%) <0.001 We performed single linear regressions to determine factors associ­
KDIGOb > 1 1–3 days 5 (16.7%) 9 (56,3%) 0.008 ated with ICU mortality and RRT. The infused fluid volumes up to 72 h
RRTc during ICUc stay 1 (3%) 10 (62,5%) <0.001
Urine output day 1 (ml/ 0.7 (0.5–1.0) 0,6 (0,3–1,2) 0.321
seem to have an association with both outcomes (Table 5 and 6).
kg/h) The main results of the study:
Creatinine on admission 69 (57–87) 91 (77–101) 0.010
(umol/l) 1) Fluid resuscitation based on the Parkland formula leads to over
Lowest BEd day 1 − 5.2 (− 7.4– − 11,9 (− 13,9– <0.001
resuscitation and potential fluid creep in the majority of patients.
(− 3.4)) (− 7,8))
Highest lactate day 1 2.1 (1.7–3.5) 6,3 (3,9–8,3) <0.001 2) The fluid volume infused during the first 24 h is associated with the
(mmol/l) fluid volume in the following 48 h, further increasing the total fluid
Hbe max day 1 (g/l) 166 (144–180) 168 (147–182) 0.466 volume.
Myoglobin on admission 138 (37–906) 932 (173–11959) 0.032 3) Higher total fluid volume administered during the first 72 h is
(ug/l)
Mortality ICUf 1 (3.3%) 6 (37,5%) 0.005
associated with higher mortality and need for RRT.
Mortality hospital 3 (10.0%) 6 (37,5%) 0.047
Mortality 12 months 3 (10.0%) 6 (37,5%) 0.047 4. Discussion
APACHE II 24 h 20.0 (14.0–25.0) 28.0 (24.3–34.5) <0.001
SAPS 24 h 34.5 (24.8–46.3) 56.5 (44.5–69.5)
We observed that excessive fluid resuscitation as defined by the Ivy
<0.001
SOFA 24 h 6.0 (3.0–8.0) 11.0 (10.0–12.8) <0.001
Baux score 84.0 (70.5–98.9) 99 (90.8–110.9) <0.001 index and urine output > 1 ml/kg/h was quite common (34.8% and
ICU length of stay 14.1 (6.5–22.0) 36,0 (18,2–64,7) 0.002 26.0% respectively). Almost half of the patients received more than
Hospital length of stay 39.0 (27.8–53.3) 59.5 (22.8–119.5) 0.076 150% of the volume predicted by the Parkland formula. Higher fluid
Fluids 0–24 h (ml) 13,237 23,543 0.002
volumes received during the first 24 h were associated with higher fluid
(9629–15094) (18118–27454)
Fluids 0–24 h (ml/kg/ 4.96 (4.45–6.38) 6.97 (5.90–8.24) <0.001 volumes received during the subsequent 48 h. A higher total fluid vol­
TBSA%) ume during the first 72 h was associated with an increased need for RRT
Fluids 0–72 h (ml) 28,827 47,068 <0.001 and increased mortality with higher fluid resuscitation volumes. Factors
(21441–32857) (39704–55438) that increased the first 24-hour fluid resuscitation volume, in addition to
Noradr. maxi 0–24 h (ug/ 0.07 (0.00–0.23) 0.18 (0.09–0.30) 0.042
TBSA% and patient weight, were inhalation injury and mechanical
kg/min)
Escharotomy within 72 h 13 (43.3%) 13 (81.3%) 0.027 ventilation on admission. Increased lactate and base deficit values were
Faschiotomy within 72 h 3 (10.0%) 5 (31.3%) 0.105 associated with higher fluid resuscitation volumes. Females were over­
Burn operation within 72 15 (50.0%) 14 (87.5%) 0.023 represented in the larger fluid volume group, which may reflect the
h
difference in comorbidities between males and females (Charlson co­
a
CCI = Charlson Comorbidity Index. morbidity index, p = 0.045). In our study, TBSA% was not associated
b
KDIGO = KDIGO criteria for acute kidney injury. with ICU mortality. One of our exclusion criteria was withdrawal of
c
RRT = Renal replacement therapy. futile intensive care within 72 h of the burn injury. Therefore, it is likely
d
BE = Base excess.
e
Hb = Haemoglobin.
f
ICU = Intensive care unit.
i
Noradr. max = Maximal noradrenalin infusion rate.

3.2. Factors associated with fluid resuscitation volume

TBSA% and patient weight were implemented in the resuscitation

formula and therefore had a significant effect on the total resuscitation
volume. In addition, presence of inhalation injury and mechanical
ventilation on admission led to increased resuscitation fluid volume
requirements. Inhalation injury was also associated with a higher fluid
rate (ml/kg/TBSA). Age and comorbidities were not associated with
fluid resuscitation volumes or rates during the first 24 h.
Of the parameters used to guide fluid resuscitation, lactate measured
on admission and the highest values of lactate and base deficit were
associated with the 24 h fluid resuscitation volume and rate (ml/kg/
TBSA). A lower urine output (ml/kg/h) on the first day was associated
with a larger resuscitation volume (p = 0.035) but urine output rate was
not associated with the resuscitation fluid infusion rate. The urine Fig. 2a. Association of urine output and fluid volume during the first 24 h.
Target range of urine output (0.5–1.0 ml/kg/h) is shown with reference lines.

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L. Lindahl et al. Burns Open 7 (2023) 51–58

et al. observed that fluid administration exceeded the Parkland predic­

tion when urine output was used as a resuscitation endpoint, but almost
half of the study population were over resuscitated, as defined by urine
output > 1 ml/kg/h. Our study demonstrated the same phenomenon.
Although there is a statistical association between the fluid resuscitation
volumes and urine output, only half of the patients’ urine output was in
the target range. In 26% of the patients the target was exceeded,
showing that the fluid infusion rate is not always titrated down based on
the urine output. This is not surprising, as the titration of the volume
resuscitation is based on several parameters in addition to diuresis,
including hemodynamic measurements, arterial blood gas analysis,
haemoglobin and lactate levels. There is often a tendency to correct
every parameter, which probably contributes to over resuscitation. The
detrimental effect of large intravenous fluid infusions on the endothelial
glycocalyx and resulting increase in vascular permeability, in addition to
the permeability disorder caused by the burn itself, may create a vicious
circle as the relative hypovolemia worsens and prompts the clinician to
Fig. 2b. Association of urine output and fluid infusion rate during the first 24
correct it by giving more fluids.
h. Target range of urine output (0.5–1.0 ml/kg/h) is shown with reference lines.
In the context of burn injury, it is usually thought that the reason for
early acute kidney injury is inadequate fluid resuscitation and resulting
Table 4 hypovolemia [5,19,42,43]. In many of the studies from the last decade
Associations with resuscitation fluid rate in the first 24 h (ml/kg/TBSA%), there is evidence that burn patients are often over resuscitated and
univariate regressions. under resuscitation is not a big problem at present [1,6,15]. There is also
evidence in other critically ill patients that positive fluid balance is an
OR (95% CI) p
independent risk factor for AKI and mortality [13,14]. Previously in the
TBSA% − 0.002 (− 0.040–0.037) 0.933
burn literature over resuscitation and AKI are related to each other in the
Age 0.013 (− 0.011–0.037) 0.285
BEa on admission − 0.077 (− 0.161–0.007) 0.070 presence of abdominal compartment syndrome [44]. We did not record
Lowest BE within 24 h − 0.126 (− 0.210–(− 0.041)) 0.004 data of intra-abdominal pressure, but there were no patients in need of
Lactate on admission 0.378 (0.058–0.698) 0.022 laparotomy because of abdominal compartment syndrome. These find­
Highest lactate within 24 h 0.287 (0.123–0.452) 0.001 ings and the evidence from the other critically ill patient groups may
Hbb on admission − 0.017 (− 0.037–0.004) 0.108
suggest that fluid overload could be an important cause of AKI also in
Highest Hb within 24 h − 0.009 (− 0.028–0.010) 0.335
Highest noradrenaline infusion rate 1.921 (0.136–3.705) 0.036 burn patients without abdominal compartment syndrome [13,14].
Urine output ml/kg/h 0–24 h − 0.013 (− 1.075–1.048) 0.980 Mitchell et al reported in 2013 that a higher resuscitation volume in
a the first 24 h correlated with a higher resuscitation volume in the next
BE = Base Excess.
b
Hb = Haemoglobin. 24 h. We analysed the fluid volumes administered during the first 72 h.
There was an association between the first 24-hour fluid volumes and
the subsequent 48-hour volumes. This finding is important, as the cu­
mulative fluid balance is a risk factor leading to complications [10].
Diminishing the net fluid balance during the first days of intensive care
can be initiated by avoiding excessive fluid resuscitation from the
beginning of resuscitation. At the time of developing Parkland and
Brooke formulas, the role of the endothelium and endothelial glycocalyx
in the permeability disorder was unknown. Studies have since shown
that intravenous fluid infusion enhances glycocalyx degradation
[45–47]. Based on these findings, supported by the association between
the first 24-hour fluid volumes and the next 24–48-hour fluid volumes
and the association between the initial fluid infusion rate and the total
resuscitation volume in the first 24 h, Parkland formula’s emphasis on
early large volume resuscitation seems potentially harmful.
Burn patients are a heterogenous group, particularly regarding burn
severity. The burn formulas apply to all 2nd and 3rd degree burn
wounds. Although the burn depth may vary and thereby impact the
systemic response and fluid demands of the patient, burn formulas do
not take this into consideration. Furthermore, in a very recent injury it is
Fig. 3. Association of the fluid resuscitation volume of the first 24 h with the often impossible to determine the depth of the wound accurately, as
fluid volume received by the patient during 24–72 h. burns tend to deepen over the first 3 days. There is also a great margin of
error in the initial estimation of the burn size when the patient is first
that some of the patients with the largest injuries were excluded from assessed outside of a specialized burn center [48]. All the aforemen­
the study, which could explain the lack of association between TBSA% tioned factors, as well as variation between individuals, makes it even
and mortality. We also found that patient age and CCI were associated more difficult to predict fluid volumes and creates the suspicion that it is
with ICU mortality. These factors may have an even more important impossible to predict the required fluid amount within a reasonable
effect on mortality than TBSA%. range based on any formula. Because of the permeability disorder,
Most of our findings are in line with earlier studies. Many of them maintaining normovolemia in a patient with a large burn injury is often
report fluid resuscitation volumes exceeding those predicted by the impossible. Therefore, the aim to normalize all hemodynamical pa­
Parkland formula in a large proportion of patients. A study by Blumetti rameters will actually lead to over resuscitation.
In our study, the cumulative fluid volumes of the first 72 h were

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Fig. 4. Boxplot showing the association between cumulative fluid volumes in 0–72 h and the need of RRT and ICU survival. The median is shown as a horizontal line
in the box and the box represents interquartile range.

Table 5 Table 6
Associations with ICU mortality (univariate regression models). Associations with RRT (univariate regression models).
Odds ratio (95% CI) p Odds ratio p

TBSA% 1.061 (0.995–1.132) 0.072 TBSA% 1.155 (1.063–1.256) <0.001

Inhalation injury 0.344 (0.064–1.859) 0.215 Inhalation injury 0.139 (0.030–0.634) 0.011
Age 1.045 (0.990–1.102) 0.013 Age 0.996 (0.960–1.033) 0.812
Charlson comorbidity index 1.383 (0.909–2.104) 0.014 Charlson comorbidity index 0.661 (0.407–1.075) 0.095
RRTa during ICUb stay 0.164 (0.030–0.903) 0.038 Hydroxycobalamin 0.118 (0.026–0.535) 0.006
Creatinine on admission 1.021 (0.996–1.046) 0.097 Creatinine on admission 1.041 (1.010–1.072) 0.008
BEc on admission 0.701 (0.548–0.896) 0.005 BEa on admission 0.871 (0.758–1.002) 0.053
BE at 24 h hours from the injury 0.778 (0.633–0.956) 0.017 BE at 24 h from the injury 0.685 (0.538–0.872) 0.002
Lactate on admission 2.269 (1.177–4.375) 0.014 Lactate on admission 2.018 (1.142–3.565) 0.016
Lactate at 24 h from the injury 1.341 (0.956–1.880) 0.089 Lactate at 24 h from the injury 1.721 (1.181–2.508) 0.005
Fluid volume 0–24 h 1.165 (1.027–1.322) 0.017 Fluids 0–24 h 1.324 (1.124–1.559) <0.001
Fluid infusion rate ml/kg/TBSA% 1.502 (0.870–2.592) 0.144 Fluid infusion rate ml/kg/TBSA% 1.445 (0.907–2.300) 0.121
Fluid volume 24–72 h 1.172 (1.037–1.325) 0.011 Fluids 24–72 h 1.256 (1.081–1.460) 0.003
Fluid volume over Ivy Indexd 1.012 (1.001–1.024) 0.030 Ivy Indexb 1.029 (1.012–1.046) 0.001
SOFA scoree 1.480 (1.084–2.021) 0.014 SOFA scorec 24 h 2.603 (1.326–5.110) 0.005
a a
RRT = Renal replacement therapy. BE = Base Excess.
b b
ICU = Intensive care unit. Ivy Index = Fluid volume 250 ml/kg/d.
c c
BE = Base Excess. SOFA Score = Sequential Organ Failure Assessment score.
d
Ivy Index = Fluid volume 250 ml/kg/d.
e
SOFA Score = Sequential Organ Failure Assessment score. for RRT.
Based on our study we concluded that there is a need to change our
associated with the need for RRT and ICU mortality. When it comes to clinical practice in burn resuscitation. Clearly our previous protocol
the burn population, the severity of the injury is a major factor in both leaded to over resuscitation in many patients. We have changed the
outcomes. The burn size is a major factor guiding the fluid resuscitation, protocol to initiate resuscitation with a reduced fluid rate and accept
as the resuscitation is commonly based on formulas taking TBSA% into that we will not reach all the resuscitation targets, as long as the patient
account. Therefore, finding the real association of the fluid volumes with does not appear to be severely hypovolemic. The aim of the resuscitation
mortality or RRT needs is difficult. should probably be permissive hypovolemia without severe organ
dysfunction. Further studies are needed to evaluate the new protocol.
5. Conclusions
6. Strengths and limitations
Our study revealed that there is a tendency to over resuscitate in our
unit. It seems that the more fluid is administered during the first 24 h, The strengths of our study include the large and reliable dataset. Our
the more fluid the patient will receive during the next 48 h. The total unit uses an electronic patient record system, where the infused fluids,
fluid amount of the first 72 h was associated with mortality and the need medication and urine output are documented hourly. The monitor data

57
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is recorded in the system automatically and the data is validated before
it is entered in the national intensive care registry.
Our study has several limitations. This was a retrospective observa­
tional study. Our study population was relatively small, and therefore
underpowered. Because of the small sample size, it was impossible to
perform multivariate analysis. We excluded delayed (>12 h) admissions
and therefore the study is not representative of all the intensive care
burn patients in our unit.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
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