Received: 19 September 2018 | Revised: 4 December 2018
DOI: 10.1111/pan.13581
RESEARCH REPORT
The association between high‐volume intraoperative fluid
administration and outcomes among pediatric patients
undergoing large bowel resection
Ethan L. Sanford1
Joseph P. Cravero1
1
Department of Anesthesiology, Critical
Care & Pain Medicine, Boston Children’s
Hospital, Boston
2
Department of Surgery, Boston Children’s
Hospital, Boston
Correspondence
Ethan L. Sanford, Department of
Anesthesiology, Critical Care & Pain
Medicine, Boston Children’s Hospital,
Boston, MA.
Email: Ethan.Sanford@utsouthwestern.edu
Section Editor: Brian Anderson
Pediatric Anesthesia. 2019;1–7.
| Accepted: 10 December 2019
| David Zurakowski1 | Anna Litvinova1 | Jill M. Zalieckas1,2 |
Abstract
Background: Traditional intraoperative fluid administration practices have been
challenged this century with data suggesting improved outcomes with restrictive or
goal‐directed fluid administration during adult bowel surgery. Minimal data on out-
comes associated with differing intraoperative fluid administration practice exists for
pediatric patients.
Aims: We assessed factors and outcomes associated with high‐volume fluid admin-
istration in pediatric patients undergoing colectomy. We hypothesized that high‐vol-
ume fluid administration is associated with impaired recovery and, thus, increased
length of stay.
Methods: A database of perioperative practice and postoperative outcomes at a
tertiary pediatric hospital was queried for colectomy encounters between July 2012
and March 2017. Data extracted included patient characteristics, perioperative clini-
cal data, and postoperative outcomes. Encounters were stratified into two groups:
greater than 90th percentile fluids administered (high‐volume fluid administration
group) vs less than 90th percentile fluids administered. Univariable tests, multivari-
able logistic regression, and propensity score matched group comparisons were used
to asses outcomes associated with high‐volume fluid administration.
Results: A total of 209 colectomy encounters were identified from which 12 were
excluded based on predetermined criteria. High‐volume fluid administration was
associated with length of stay >6 days (AOR 8.14, CI 1.75‐37.8, P = 0.007), time to
first meal >4 days (AOR of 5.91, CI 1.30‐27.17, P = 0.02), and supplemental oxygen
requirement >24 hours (AOR 3.60, CI 1.25‐10.39, P = 0.02) after adjusting for ASA
status, blood loss, transfusion, and open surgery. Similarly, propensity score matched
patients with high‐volume fluid administration vs controls were more likely to have
length of stay >6 days (93% vs 54%, P = 0.007), time to first meal >4 days (93% vs
57%, P = 0.009), and supplemental oxygen requirement >24 hours (36% vs 12%,
P = 0.033).
Conclusion: High‐volume fluid administration during colectomy for pediatric
patients is associated with worsened postoperative outcomes suggestive of impaired
recovery.
wileyonlinelibrary.com/journal/pan © 2019 John Wiley & Sons Ltd | 1
2 | SANFORD ET AL.

KEYWORDS
colorectal surgery, edema, fluid therapy, length of stay, pediatric, postoperative complications

1 | INTRODUCTION
The goals of perioperative fluid management are to achieve normov- What is already known
olemia, preserve tissue perfusion, and maintain electrolyte balance.  Traditional intraoperative intravenous fluid management
Methods to achieve these goals, including the “4‐2‐1” rule for main-
practices have been challenged as restrictive and goal‐di-
tenance fluid requirement based on calculations of metabolic
rected fluid administration in adult surgical patients is
requirements, were primarily developed in the1950s‐1970s.1,2 These
associated with decreased surgical complications,
methods are frequently used, yet clinical data showing benefit to
improved cardiovascular and pulmonary outcomes,
patient outcomes are lacking.3
decreased length of stay, and even mortality benefit.
Traditional fluid management strategies have been challenged as
more recent data have demonstrated improved outcomes with goal‐di-
What this article adds
rected fluid administration targeting specific indicators of fluid respon-
 For pediatric patients undergoing colectomy, we identify
siveness or restrictive fluid administration. The vast majority data
supporting these fluid management strategies were generated in adult an association between high‐volume intraoperative fluid
patients.4–7
Both restrictive and goal‐directed fluid therapy strategies administration and increased length of stay, time to first
have been incorporated into Enhanced Recovery After Surgery (ERAS) meal, and postoperative supplemental oxygen require-
protocols which are intended to minimize stress responses to surgery. ment.
In randomized trials, initiation of ERAS protocols has been shown to
decrease cardiovascular and pulmonary complications after colorectal
surgery and intra‐abdominal non‐colorectal surgery.8–10
primary diagnosis leading to colectomy, surgical procedure, and
Despite the rapid transformation in fluid administration among
American Society of Anesthesiology (ASA) status. Intraoperative data
adult surgical patients, there is a relative dearth of data on perioper-
extracted included duration of anesthetic, fluids administered, colloid
ative fluid administration practices for children. This study aimed to
or blood products transfused, percentage of time hypotensive (sys-
specifically assess intraoperative factors and outcomes associated
tolic blood pressure greater than 20% below baseline), regional anes-
with patient encounters wherein fluid administration was in the top
thesia use, estimated blood loss (EBL), urine output, and fasting time.
10th percentile. We hypothesized that high‐volume fluid administra-
Outcomes assessed included postoperative LOS, duration of
tion would be associated with worsened postoperative outcomes,
postanesthesia care unit stay, time to first meal, unplanned readmis-
primarily increased length of stay (LOS).
sion within 30 days, supplemental oxygen requirement greater than
24 hours, and significant chest X‐ray findings (defined as pulmonary
2 | MATERIALS AND METHODS effusion, pneumonia, pulmonary edema).

2.1 | Data source

After IRB approval, Current Procedural Terminology codes were
used to identify surgical cases which included colectomy. We then
used our previously described Integrated Outcomes Database 11
to
extract patient characteristics, intraoperative, and postoperative data
from anesthetic records. Individual patient charts were analyzed to
determine outcomes not readily available from the database. All
cases occurred in a single tertiary pediatric hospital.
2.2 | Population data extracted
The study population included all pediatric patients (less than
21 years) undergoing colectomy. Encounters involving emergent pro-
cedures and patients with cardiac disease or renal disease were
excluded. Patient characteristics extracted included age, sex, weight,
2.3 | Standardized fluid administration calculation
In order to provide a basis for comparative fluid administration, each
patient's total fluids were calculated as crystalloid + (colloid × 1.5).
To adjust for surgical duration, the maintenance rate as determined
by standard 4‐2‐1 rule1 was multiplied by surgical time and this pro-
duct was subtracted from total fluids. The adjusted total fluids
administered were divided by maintenance rate to normalize for
patient size‐related metabolic requirements. The derived unit for
standardized fluids administered is hours of maintenance fluids. As
an example, for a 60‐kg patient who undergoes a 4‐hour procedure
and receives 1 L of lactated ringers and 500 mL of 5% albumin, the
calculation would be as follows: [1000 mL + (500 mL × 1.5) − (100
mL/h × 4 h)]/100 mL/h = 13.5. For this child, 13.5 hours of mainte-
nance fluids is equivalent to 13.5 h × 100 mL/h = 1350 mL of fluid.
SANFORD ET AL. | 3

first meal for the high‐volume fluid administration group vs the rest
2.4 | Statistical analysis
of the patients. Differences between median fluids given to patients
who required supplemental oxygen need greater than 24 hours post-
2.4.1 | Baseline characteristics
operatively vs those who did not were assed with Mann‐Whitney
Baseline characteristics for all the patient encounters were estab- test.
lished with median values with interquartile ranges reported for con-
tinuous variables and percentages for categorical variables.
2.4.5 | Propensity score matching
Encounters were stratified into two groups: high‐volume fluid admin-
istration group with greater than 90th percentile fluids vs patients Propensity score matching was performed with the PSMATCH2
who received less than 90th percentile fluids. command in Stata 15.0. An 8:1 matching algorithm using logistic
regression with nearest neighbor matching was used to achieve bal-
ance between patients in the high‐volume fluid administration group
2.4.2 | Univariable associations between high‐
and all other patients based on four confounders: EBL, ASA status,
volume fluid administration and patient
open procedure, and procedure time. The matched groups were then
characteristics, intraoperative factors, and patient
assessed for differences in binary outcomes (LOS greater than
outcomes
6 days, time to first meal greater than 4 days, and supplemental oxy-
Univariable differences between the high‐volume fluid administration gen need greater than 24 hours) with chi‐square test.
group and the rest of the cohort were assessed for significance with
Mann‐Whitney test for nonparametric continuous variables and chi‐
3 | RESULTS
square test for categorical variables.

3.1 | Study population characteristics

2.4.3 | Association between high‐volume fluid
administration and length of stay
The primary endpoint of interest was hospital LOS from the time of
surgery and the primary independent variable was standardized flu-
ids administered in hours of maintenance fluid.
Patient encounters were separated into quintiles based on fluids
administered. Differences in LOS for patients in the fluid quintile
groups were assessed with the Kruskal‐Wallis rank test for nonpara-
metric data.
Linear regression modeling was used evaluate change in LOS for
each unit change in standardized fluids with corresponding 95% con-
fidence intervals. The Spearman rho correlation coefficient between
amount of fluids given and LOS was calculated. Multivariable logistic
regression was applied with the likelihood ratio test to assess predic-
tors and covariates adjusted for in the modeling.12 A cutoff based
on the median was used to create a binary outcome for hospital
LOS greater than 6 days. Multivariable logistic regression determined
the adjusted odd ratios (AOR) for LOS greater than 6 days with the
covariables high‐volume fluid administration, EBL, PRBC transfusion,
Between July 2012 and March 2017, 209 unique encounters were
identified from which 12 were excluded. In seven cases, the surgical
procedure did not include colectomy or there was incomplete data,
three cases were emergent, and two cases involved patients with
significant renal or cardiac disease. The baseline demographic and
perioperative characteristics for these patient encounters were
determined (Table 1). Specific types of fluids for all patient encoun-
ters (N = 197) included: 193 lactated ringers, 35 normal saline, 35
albumin 5%, 23 parenteral nutrition, and 7 plasmalyte. There was
insufficient data to determine fasting time for a majority of patients
preventing calculation of an accurate fluid deficit.
T A B L E 1 Patient characteristics
N = 197
Age (y) 15.8 (11.9‐17.7)a
Weight (kg) 53.9 (39.6‐64)a
Sex 58% vs 42%
Inflammatory bowel disease 141(71.5%)

ASA status, and open procedure. Laparoscopic 164 (83.2%)

UOP (mL/kg/h) 1.0 (0.63‐1.74)a
ASA 3 or 4 63 (33%)
2.4.4 | Association between high‐volume fluid
EBL (mL/kg) 0.6 (0.2‐1.7)a
administration and secondary outcomes
Regional 168 (85%)
A cutoff based on the median was used to create a binary outcome Procedure time (h) 6.1(4.6‐7.8)a
for time to first meal greater than 4 days. Multivariable logistic PRBC transfusion 6 (3.0%)
regression determined the AOR separately for time to first meal HMF 16.5 (10.5‐24.5)a
greater than 4 days and supplemental oxygen requirement greater
ASA, American Society of Anesthesiologists physical status classification;
than 24 hours with the covariables high‐volume fluid administration,
EBL, estimated blood loss; HMF, Hours of Maintenance Fluids; PRBC,
EBL, PRBC transfusion, ASA status, and open procedure. Kaplan‐ packed red blood cell; UOP, urine output.
a
Meier analysis was used to further describe differences in time to Median value (IQR).
4 | SANFORD ET AL.

for each 1 hour increase in fluids (beta coefficient = 0.12, CI 0.07‐

3.2 | Univariable associations between high‐volume
fluid administration and patient characteristics,
intraoperative factors, and patient outcomes
The high‐volume fluid administration group received a median of
39.4 hours of maintenance fluids compared to 15.1 in the other
patient encounters. High‐volume fluid administration was signifi-
cantly associated with longer anesthetic time and increased EBL
(Table 2, P < 0.001 for both).
Patients in the high‐volume fluid administration group experi-
enced increased LOS (7.3 vs 5.4 days, P < 0.001), time to first meal
(5 days vs 4 days, P < 0.001), and supplemental oxygen use greater
than 24 hours (45% vs 14.1%, P < 0.001) (Table 2).
3.3 | Association between high‐volume fluid
administration and LOS
For the primary outcome, LOS, there were significant differences
between patients grouped by quintiles of fluids (P < 0.001) (Fig-
ure 1A). Linear regression revealed an increase in LOS of 0.12 days
0.17, P < 0.001) (Figure 1B), which yields an estimated increase of
one additional day in hospital for every 8.3 additional hours of main-
tenance fluids administered. The Spearman rho correlation showed
association between the amount of fluids given and LOS (Spearman
rho = 0.37, P < 0.001). High‐volume fluid administration was associ-
ated with LOS greater than 6 days (AOR 8.14, CI 1.75‐37.8,
P = 0.007) after adjusting for ASA status, EBL, PRBC transfusion,
and open procedure (Table 3).
3.4 | Association between high‐volume fluid
administration and secondary outcomes
High‐volume fluid administration was associated with time to first
meal greater than 4 days (AOR of 5.91, CI 1.30‐27.17, P = 0.02)
(Table 3) after adjusting for confounders. Patients in the high‐volume
fluid administration group had increased time to first meal as com-
pared to the rest of patients in Kaplan‐Meier analysis (Log rank
test = 7.18, P = 0.007) (Figure 2A).

T A B L E 2 Univariable associations
High‐volume FA <90th percentile P
(n = 20) FA (n = 177) Value
HMF 39.4 (35.5‐43.8)a 15.1 (9.7‐22.4)a <0.001
Age (y) 14.8 (12.7‐16.9)a 15.9 (11.8‐17.8)a 0.54
ASA 3 or 4 8 (40%) 55 (31.1%) 0.42
Inflammatory bowel 17 (85%) 125 (70.6%) 0.16
disease
Open surgery 3 (15%) 34 (19.2%) 0.65
Regional use 19 (94%) 148 (83.6%) 0.18
Percent intraoperative 3.9 (0‐18.3)a 1.3 (0‐5.6)a 0.09
time hypotensive
UOP (mL/kg/h) 1.5 (0.7‐2.0)a 1.0 (0.6‐1.7)a 0.28
EBL (mL/kg) 1.9 (0.9‐4.7) a
0.5 (0.2‐1.4) a
<0.001
Procedure time (h) 9.3 (7.7‐10.9)a 5.8 (4.3‐7.4)a <0.001
PRBC transfusion 2 (10%) 4 (2.3%) 0.06
Length of stay (d) 7.3 (8.2‐11.3)a 5.4 (4.3‐7.1)a <0.001
Time to first meal (d) 5 (4‐6.5)a 4 (3‐5)a 0.008
a
PACU duration (min) 105 (84‐117) 96 (69‐125)a 0.67
Supplemental oxygen 9 (45%) 25 (14.1%) <0.001
>24 h
Readmission within 5 (25%) 22 (12.4%) 0.12
30 d
Significant chest X‐ 3 (15%) 10 (5.6%) 0.11
ray finding

ASA, American Society of Anesthesiologists physical status classification;

EBL, estimated blood loss; FA, fluid administration; HMF, Hours of Main-
tenance Fluids; PACU, Postanesthesia; PRBC, packed red blood cell;
UOP, urine output.
P values determined using Mann‐Whitney test for nonparametric contin-
uous variables and chi‐square test for categorical variables.
a
Median value (IQR).
F I G U R E 1 Association of high‐volume fluid administration with
increased length of stay (LOS). (A) Boxplot demonstrating medians
with interquartile ranges for LOS (y axis) vs Hours of Maintenance
Fluids (HMF) in quintile groups (x axis). (B) Linear regression fit line
for length of stay against HMF
SANFORD ET AL. | 5

T A B L E 3 Multivariable logistic regression analysis

Adjusted Odds Ratio (95% CI) P Value
Length of stay >6 days
High‐volume FA 8.14 (1.75‐37.80) 0.007
ASA 3 or 4 2.67 (1.38‐5.17) 0.004
EBL (mL/kg) 1.21 (1.01‐1.45) 0.04
PRBC transfusion 1.01 (0.13‐7.72) 0.99
Open surgery 1.67 (0.76‐3.69) 0.20
Time to first meal >4 days
High‐volume FA 5.91 (1.30‐27.17) 0.02
ASA 3 or 4 1.60 (0.83‐3.17) 0.16
EBL (mL/kg) 1.09 (0.93‐1.27) 0.29
PRBC transfusion 0.79 (0.12‐5.22) 0.81
Open surgery 1.44 (0.66‐3.20) 0.46
Supplemental oxygen >24 h
High‐volume FA 3.60 (1.25‐10.39) 0.018
ASA 3 or 4 1.10 (0.47‐2.56) 0.83
EBL (mL/kg) 1.17 (1.01‐1.35) 0.04
PRBC transfusion 0.54 (0.05‐5.96) 0.62
Open surgery 0.41 (0.12‐1.47) 0.17

ASA, American Society of Anesthesiologists physical status classification;

EBL, estimated blood loss; FA, Fluid administration; PRBC, packed red
blood cell.

High‐volume fluid administration was associated with increased

supplemental oxygen need postoperatively (AOR 3.60, CI 1.25‐
10.39, P = 0.02) after adjusting for confounders (Table 3). Patients
with supplemental oxygen need greater than 24 hours received a
median of 22.2 hours maintenance fluids vs 15.6 in those without
supplemental oxygen need (P < 0.001) (Figure 2B).
F I G U R E 2 Association of high‐volume fluid administration with
increased time to first meal and supplemental oxygen need. (A)
Kaplan‐Meier plot demonstrating increased time to first meal in the
high‐volume fluid administration group versus all other patient
encounters. (B) Box plot depicting median Hours of Maintenance
Fluids to patients who needed supplemental oxygen for less than or
greater than 24 hrs

3.5 | Propensity score matching

Propensity score matching yielded 109 control patients matched to
T A B L E 4 Comparison of outcomes between patients in high‐
14 patients in the high fluid administration group. Standardized mean
volume FA group and rest of patients: propensity score matching
differences (d values) in confounders between groups were all <0.10
High‐volume <90th percentile P
indicating good balance of confounders between groups post match-
Outcome FA (N = 14) FA (N = 109) Value
ing. Patients with high fluid administration vs matched controls were
Length of stay 13 (93%) 59 (54%) 0.007
more likely to have LOS greater than 6 days (93% vs 54%,
>6 days, N (%)
P = 0.007), time to first meal greater than 4 days (93% vs 57%,
Time to first meal 13 (93%) 62 (57%) 0.009
P = 0.009), and supplemental oxygen need greater than 24 hours >4 days, N (%)
(36% vs 12%, P = 0.03) (Table 4). Supplemental oxygen 5 (36%) 13 (12%) 0.03
>24 h, N (%)

4 | DISCUSSION FA, Fluid administration.

In this retrospective cohort study, we identify an association

between copious intraoperative fluid administration and worsened
outcomes. This is in line with a majority of adult data. Our findings
suggest that traditional intraoperative fluid practices can lead to
high‐volume fluid administration and that high‐volume fluid adminis-
tration is associated with impaired recovery after colectomy for
pediatric patients.
Minimal data are available to describe variation in perioperative
fluid administration practices in pediatric surgery or the effect of
variance on patient outcomes. Most published data have focused on
variability in dextrose and salt concentrations.13 Evidence relating to
intraoperative fluid volume administration includes a prospective
study of 23 children less than 3 years old undergoing abdominal
6 |
surgery where omitting replacement of interstitial fluid loss (esti-
mated at 5 mL/kg/h) led to increased need for fluid bolus and nega-
tive base deficit without effect on time to return of bowel
14
function. In pediatric trauma patients, increased fluid administra-
tion is associated with increased ventilator days, ICU stay, time fast-
ing, and overall hospital LOS.15,16 The limited data on ERAS
implementation with fluid restriction for pediatric patients have
demonstrated improved outcomes including decreased LOS and
improvement in bowel function without any associated complica-
tions.17–19
Excess fluid administration may cause adverse outcomes due to
several unfavorable effects. Isotonic fluid administration results in
increased hydrostatic pressure and decreased oncotic pressure. Con-
sequently, water disperses into the extravascular spaces. This is com-
monly referred to as fluid edema which has been demonstrated to
depress tissue and cellular function. Bowel edema is known to result
in abnormal peristalsis and, in animal models, decreases the stability
of bowel anastomosis.20 Several human clinical studies have also
found liberal fluid administration results in increased rates of anasto-
motic leak, wound infection, and other surgical complications.21,22
Delayed return of bowel function negatively impacts patient nutri-
tion, recovery, and hospital LOS.8,23 Pulmonary edema is also associ-
ated with excess fluid administration. More recently, a meta‐analysis
showed that liberal fluid administration in the perioperative period is
24
associated with increased risk of pneumonia. Caution must be
taken, however, as recent studies of older adults with significant
comorbid conditions showed increased propensity for renal injury
with fluid restriction strategies.25
In this study, there was wide variation in intravenous fluid man-
agement as demonstrated by a two‐ to threefold increase in median
fluids given to the high‐volume fluid administration group as com-
pared to the rest of the patient encounters. The variance in fluid
administration volume may be due to variance in traditional manage-
ment guidelines set forth by training programs and anesthesia litera-
3
ture over time. We assessed clinical factors traditionally used to
guide fluid administration and determined blood loss and the length
of procedure were the only factors associated with high‐volume fluid
administration.
We used postoperative LOS as a primary outcome because it is
related to general patient recovery. Our finding of increased LOS
associated with high‐volume fluid administration may be secondary
to worsened pulmonary and gastrointestinal function. This is sup-
ported by our secondary outcome findings of increased time to first
meal and need for supplemental oxygen in those patients who
received higher amounts of fluid. These associations were indepen-
dent of the possible confounders blood loss, PRBC transfusion, open
procedure, general patient disease burden as determined by ASA sta-
tus, and procedure length.
Our study has several imitations, the most prominent of which is
the inability to control for all possible confounders. Confounders such
as surgical complexity, severity of disease state, and type of bowel
preparation have not been standardized and were not readily avail-
able from our database or medical record. Some perioperative data
SANFORD ET AL.
such as fasting time and patient comorbid conditions were either not
available or not readily extracted in a significant portion of encoun-
ters which made assessment of these factors not possible. Addition-
ally, some data such as estimation of intraoperative EBL may be
imprecise. Our study population consisted mostly of adolescents
making generalizability to infants and young toddlers uncertain.
Despite these limitations, the association between fluid adminis-
tration and the primary variable LOS was statistically significant even
when controlling for confounders through both multivariable logistic
regression and propensity score matching. Additionally, the clinical
difference between groups for the primary outcome was substantial
with a 3‐day longer median LOS for patients in the high‐volume fluid
administration group. These findings suggest impaired recovery when
there is large volume intravenous fluid given intraoperatively. Avoid-
ance of excess fluid administration may be achieved by restrictive
fluid management, earlier use of vasoconstrictors to counteract
vasodilatory effects of anesthetics, or goal‐directed fluid administra-
tion based on dynamic measurements associated with fluid respon-
siveness. Further prospective investigations focused on the safety
and outcome benefits of differing fluid management practices either
independently or as part of an ERAS protocol are certainly warranted.
ETHICAL APPROVAL
Internal Review Board obtained through Boston Children's Hospital.
CONFLICT OF INTEREST
Joseph P Cravero is a section editor for Pediatric Anesthesia.
ORCID
Ethan L. Sanford https://orcid.org/0000-0002-7423-6521
Joseph P. Cravero https://orcid.org/0000-0003-0629-6511
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How to cite this article: Sanford EL, Zurakowski D, Litvinova
A, Zalieckas JM, Cravero JP. The association between high‐
volume intraoperative fluid administration and outcomes
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