Pancreatology xxx (2018) 1e6

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Pancreatology
journal homepage: www.elsevier.com/locate/pan

Comparison of normal saline versus Lactated Ringer's solution for fluid

resuscitation in patients with mild acute pancreatitis, A randomized
controlled trial
Sararak Choosakul, Kamin Harinwan, Sakkarin Chirapongsathorn, Krit Opuchar,
Theeranun Sanpajit, Wanich Piyanirun, Chaipichit Puttapitakpong*
Division of Gastroenterology and Hepatology, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand

a r t i c l e i n f o a b s t r a c t

Article history: Background/Objectives: Aggressive fluid resuscitation is recommended for initial management of acute
Received 1 December 2017 pancreatitis. However, there are few studies which focus on types of fluid therapy.
Received in revised form Methods: We performed a randomized controlled trial in patients with acute pancreatitis. The patients
27 April 2018
were randomized into two groups. Each group received Normal Saline solution (NSS) or Lactated Ringer's
Accepted 28 April 2018
Available online xxx
solution (LRS) through a goal-directed fluid resuscitation protocol. Systemic inflammatory response
syndrome (SIRS) at 24 and 48 h, mortality, presence of local complications and inflammatory markers
were measured.
Keywords:
Acute pancreatitis
Results: Forty-seven patients were included. Twenty-four patients (51%) received NSS and 23 patients
Normal saline received LRS. There was significant reduction in SIRS after 24 h among subjects who resuscitated with
Lactated Ringer LRS compared with NSS (4.2% in NSS, 26.1% in LRS, P ¼ 0.02). However, SIRS reduction at 48 h was not
Fluid resuscitation different between groups (33.4% in NSS, 26.1% in LRS, P ¼ 0.88). Mortality was not different between NSS
SIRS and LRS (4.2% in NSS, 0% in LRS, P ¼ 1.00). CRP, ESR and procalcitonin increased at 24 h and 48 h after
admission with no difference between the two groups. Local complications were 29.2% in NSS and 21.7%
in LRS (P ¼ 0.74). The median length of hospital stay was not significantly different in the two groups (5.5
days in NSS, 6 days in LRS, P ¼ 0.915).
Conclusions: Lactated Ringer's solution was superior to NSS in SIRS reduction in acute pancreatitis only in
the first 24 h. But SIRS at 48 h and mortality were not different between LRS and NSS.
© 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

1. Introduction [2e4]. Currently, crystalloids are recommended as the initial

One of the most common diseases of the digestive system which
have high mortality despite treatment is acute pancreatitis. Recent
studies showed that the incidence of disease varies between 4.9
and 73.4 cases per 100,000 population worldwide and is caused by
gallstone (40e70%) and alcohol (25e35%) [1].
The key management in acute pancreatitis, especially in the
early hours of the disease is aggressive fluid therapy. It can reduce
mortality and severe local complication such as pancreatic necrosis
Abbreviations: BUN, blood urea nitrogen; CRP, C-reactive protein; ERCP, endo-
scopic retrograde cholangiopancreatography; ESR, erythrocyte sedimentation rate;
LRS, Lactated Ringer's solution; NSS, normal saline solution; SIRS, systemic in-
flammatory response syndrome.
* Corresponding author.
E-mail address: chaipichit_p@pcm.ac.th (C. Puttapitakpong).
resuscitation fluids in patients with acute pancreatitis. However,
the optimal fluid types for resuscitation is still unclear and the most
appropriate volume for the treatment of acute pancreatitis is still
debatable [2,4].
Normal Saline solution (NSS), an isotonic crystalloid solution
(osmolarity 308 mOsm/L) with a nominal pH of 5.5, is commonly
used as the first-line fluid treatment for the patients with acute
pancreatitis [5,6]. However, infusion of large volumes of NSS can
finally lead to development of a hyperchloremic metabolic acidosis
which can increase mortality and local complication. Moreover,
acute pancreatitis may have already developed metabolic acidosis
from impaired renal function. The balanced crystalloid Lactated
Ringer's solution (LRS) may be more beneficial than NSS in reducing
the risk of hyperchloremic metabolic acidosis from resuscitation.
Furthermore, lactate is metabolized by the liver into bicarbonate,
which can improved metabolic acidosis from acute pancreatitis.

https://doi.org/10.1016/j.pan.2018.04.016
1424-3903/© 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Please cite this article in press as: Choosakul S, et al., Comparison of normal saline versus Lactated Ringer's solution for fluid resuscitation in
patients with mild acute pancreatitis, A randomized controlled trial, Pancreatology (2018), https://doi.org/10.1016/j.pan.2018.04.016
2 S. Choosakul et al. / Pancreatology xxx (2018) 1e6
A previous open-label randomized controlled trial suggested
that fluid resuscitation with LRS may be associated with reduced
inflammation when compared to NSS [7]. However, there are very
few studies which focus on the types of fluid therapy used in
treating acute pancreatitis. Therefore, this study was designed to
investigate the effects of different types of fluids used for patients
with acute pancreatitis.
2. Methods
2.1. Study design
This was a single-center, prospective, randomized controlled
trial conducted in Phramongkutklao hospital, Bangkok, Thailand.
Phramongkutklao hospital is a 1200-bed tertiary care center and
pancreatic center. The study was approved by the Hospital Review
Board of Medical Ethics and was registered with clinicaltrials.in.th
(TCTR20161010001). All authors had access to study data and
reviewed and approved the final manuscript.
2.2. Study participants
This study population consisted of patients chosen consecu-
tively, 18e80 years old, who were admitted to the hospital with
acute pancreatitis which was diagnosed in accordance with the
Revised Atlanta classification [8]. The diagnosis of acute pancrea-
titis requires two of the following three features: (1) abdominal
pain consistent with acute pancreatitis (2) serum lipase activity (or
amylase activity) at least three times greater than the upper limit of
normal; and (3) characteristic findings of acute pancreatitis on
contrast-enhanced computed tomography or magnetic resonance
imaging. Patient enrollment went from November 2015 to
December 2016. Exclusion criteria were post endoscopic retrograde
cholangiopancreatography (ERCP) pancreatitis, transfer from other
hospital, history of severe cardiovascular, respiratory, renal, he-
patic, hematologic or immunologic conditions as defined as greater
than those defined for New York Heart Association class II heart
failure, active myocardial ischemia, cardiovascular intervention
within previous 60 days, history of cirrhosis, chronic kidney disease
with creatinine clearance < 40 mL/min, chronic obstructive pul-
monary disease with requirement for home oxygen and hypercal-
cemia. Patients with a history of metastatic malignancy,
autoimmune disease, chronic infectious disease including human
immunodeficiency virus or tuberculosis, acute cholangitis, acute
cholecystitis, bowel ischemia or bowel perforation were also
excluded due to increased systemic inflammation.
2.3. Recruitment procedures
Potentially eligible patients were approached at initial assess-
ment in the emergency department for study inclusion. Acute
pancreatitis was diagnosed by attending staff physician and was
confirmed by a study staff physician. Door to fluid infusion time was
within 1 h after presentation at the emergency department. All
research subjects gave informed consent.
2.4. Study intervention
Participants were randomized into two groups using the tech-
nique of permuted block randomization with random block sizes of
4. Group 1 received NSS and group 2 received LRS. Opaque, sealed
envelopes were numbered consecutively, and all the sealed enve-
lopes were prepared by a research nurse who was not involved in
the treatment procedure. After informed consent was obtained, an
envelope was opened by the researcher according to the patient's
Please cite this article in press as: Choosakul S, et al., Comparison of normal saline versus Lactated Ringer's solution for fluid resuscitation in
patients with mild acute pancreatitis, A randomized controlled trial, Pancreatology (2018), https://doi.org/10.1016/j.pan.2018.04.016
order of entry into the trial, and the assigned treatment was offered
to the participant. Participants were blinded to treatment alloca-
tion. Fluid resuscitation was mostly given through peripheral line.
Except for cases with organ failure, they were transferred to the
intensive care unit. Fluid might also be given through a central line.
It depended on the decision of intensivist.
Each participant received fluid resuscitation in accordance with
a goal-directed protocol developed by Wu et al. [7] (Supplementary
Fig. 1). First, either 20 mL/kg of NSS or LRS was initially, rapidly
administered within 30 min (e.g. 1200 mL for 60-kg individual),
followed by continuous infusion of 3 mL/kg/h (e.g. 180 mL/h for 60-
kg individual). Physicians reevaluated patients with a bedside
clinical examination and repeated blood urea nitrogen (BUN)
measurement after 8e12 h (check point 1) and 16e20 h (check
point 2).
Participants whose BUN level remain unchanged or increased
BUN level were classed as fluid refractory group while participants
with decreased BUN level were classed as fluid responsive group.
Participants in fluid refractory group received a 20 mL/kg of fluid
loading and followed by continuous infusion of 3 mL/kg/h. Partici-
pants in fluid responsive group did not receive further fluid loading
but continued to receive fluid infusion with a decreased rate of
1.5 mL/kg/h (e.g., 90 mL/h for 60-kg individual). The patients were
re-evaluated for systemic inflammatory response syndrome (SIRS)
at 24 and 48 h after resuscitation. Bio-inflammatory markers were
re-collected at 48 h. The in-hospital mortality rate and 30-day
mortality rate were evaluated.
If the patients were diagnosed with mild acute pancreatitis, the
fluid was given for only 24 h after hospital admission in accordance
with the goal-directed protocol. If the patients diagnosed with se-
vere acute pancreatitis, the fluid resuscitation was given in the first
24 h in accordance with the goal-directed protocol and then vol-
ume and type of the fluid after 24 h depended on the decision of the
intensivist.
2.5. Outcome measurement
Primary outcome was assessed by SIRS reduction in patients
with acute pancreatitis at 24 h and 48 h after initial fluid resusci-
tation and treatment with either NSS or LRS as compared to levels
prior to resuscitation. SIRS was defined as the presence of 2 of the
following criteria: pulse >90 beats/min; respirations >20/min or
PaCO2 < 32 mm Hg; temperature <36  C or >38  C; white blood cell
count <4000 cells/mm3 or >12,000 cells/mm3 or >10% band forms
[9].
The participants' information included demographic data, basic
laboratory investigation and bio-inflammatory markers (C-reactive
protein, CRP; procalcitonin; erythrocyte sedimentation rate, ESR)
were collected before initial fluid infusion. Bio-inflammatory
markers were collected again after 48 h.
Secondary outcomes were in-hospital mortality and 30-day
mortality, organ failure (P/F ratio  300, creatinine  1.9 mg/dL and
systolic blood pressure < 90 mmHg after fluid resuscitation) and
reduction in bio-inflammatory marker (CRP, procalcitonin and
ESR). There were no outcome measure changes after trial
commencement.
Local complications were evaluated with computed tomography
(CT) of the abdomen. Computed tomography of the abdomen was
performed at 72e96 h after onset of symptoms if the patient failed
to response to conservative treatment or showed clinical
deterioration.
2.6. Data safety and monitoring
An independent data safety committee consisting of 2
 S. Choosakul et al. / Pancreatology xxx (2018) 1e6 3

independent gastroenterologists, and a biostatistician monitored
patient safety while the study was in progress. All serious adverse
events occurring during the study were evaluated by the commit-
tee in 48e72 h. Some protocol modification were recommended by
the committee.
The committee's recommendation was mainly about the volume
of fluid resuscitation. If the patients received some amount of the
fluid followed the protocol but the other parameters (such as urine
output, CVP or IVC variation) which were measured by intensivist
were not good, the safety monitoring committee recommended
giving some fluid loading (out of protocol) to the patients.
3.2. Effect of the type of fluid resuscitation on SIRS
SIRS before fluid resuscitation were not significantly different
between the two groups (41.7% in NSS vs 34.8% in LRS, P ¼ 0.846).
Median value of SIRS before resuscitation was 1 (interquartile
range, IQR, 0 and 2). At 24 h after resuscitation, SIRS were signifi-
cantly reduced among subjects resuscitated with LRS when
compared to NSS (4.2% in NSS, 26.1% in LRS, P ¼ 0.02). However,
SIRS reduction at 48 h when compare to before fluid resuscitation
was not significantly different for the two types of fluid resuscita-
tion (33.4% in NSS, 26.1% in LRS, P ¼ 0.88) (Table 2).

3.3. Other outcomes and adverse events

2.7. Statistical analysis
According to a previous study, SIRS reduction in treatment with
Lactated Ringer's solution was 84% (95% CI: 62.1%e96.8%)
compared to 0% with a Normal Saline solution (95% CI: 0% to 16.8)
[7]. We calculated that 46 patients (23 per study group) would
provide a power of at least 95% on the basis of Fisher's exact test,
with a two-sided significance level of 0.05.
Age, sex and underlying disease was shown through descriptive
report of frequency, percent, mean and standard deviation.
Between-group differences in gender, age and blood pressure were
analyzed using a t-test and chi-square test for independent sam-
ples. A P-value of less than 0.05 indicated a statistically significant
difference. No interim analyses are reported in this study.
3. Results
3.1. Study population
This study took place from November 2015 to December 2016 as
originally planned. We initially recruited 52 patients. However, five
patients were excluded for several reasons (Supplementary Fig. 2).
The remaining forty-seven patients were randomized into two
groups. Twenty-four patients were treated with NSS and twenty-
three patients were treated with LRS. No patient was lost to
follow-up. All 47 participants were included in the analysis. The
mean age of patients was 51.6 years (SD, standard deviation, 16.99)
and 61.5% were male. The mean time from onset of symptoms to
inclusion was 8.96 h (SD, 5.02). The main etiology of pancreatitis
was gallstone in both groups. Overall, the patients in each group
were similar in age, gender, body weight, etiology of pancreatitis.
(Table 1).
At 48 h after resuscitation, all of bio-inflammatory markers (CRP,
ESR and procalcitonin) increased compared to the baseline but
there was no statistical difference between the group with NSS and
the group with LRS (Table 3).
Median length of stay was not significantly different between
two groups (5.5 days with 4 and 9 interquartile range; IQR in NSS, 6
days with 4 and 9 IQR in LRS, P ¼ 0.915). Mean of total volume in the
first 24 h was 5156 mL which was not different between NSS and
LRS groups. There was no report of pulmonary edema or volume
overload after resuscitation (Table 4). There were 2 patients in NSS
group and only one patient in LRS group who were classed as fluid
refractory at check point 1. There was only one patient in NSS group
and none in LRS group who was classed as fluid refractory at check
point 2.
Local complications occurred in 15 of 47 (31.9%) patients. The
most common local complication was peripancreatic fluid collec-
tion which occurred in 11 of 47 (23.4%) patients. Pancreatic necrosis
was found in only 2 patients from the NSS group. Late local com-
plications (pseudocyst and walled-off necrosis) occurred in only
one patient from each group. Overall, local complications were not
different between groups. Local complication occurred only in the
patients with organ failure at admission.
One patient from the NSS group developed organ failure which
persisted for 48 h after admission. This patient experienced mul-
tiple organ failure (cardiac failure, respiratory failure, and renal
failure). In contrast, one patient from LRS group developed only
respiratory failure.
Mild, moderately severe, and severe severity which defined by
revised Atlanta classification [8] were 63.83%, 31.91%, and 4.26%,
respectively. There is no statistical difference between NSS and LRS
group.
Only one patient, which was assigned to receive NSS, died

Table 1
Baseline characteristic and clinical features of patients in Normal Saline and Lactated Ringer's solution.

NSS (n ¼ 24) LRS (n ¼ 23) P-value

Gender Male 17 (70.8%) 12 (52.2%) 0.188

Female 7 (29.2%) 11 (47.8%)
Age (years) (mean ± SD) 48.33 ± 13.56 54.78 ± 20.42 0.225
Duration of symptoms (hr) (mean ± SD) 8.63 ± 4.76 9.3 ± 5.36 0.648
Etiology Alcohol 7 (29.2%) 8 (34.8%) 0.91
Gall stone 15 (62.5%) 13 (56.5%)
Others 2 (8.3%) 2 (8.7%)
Body weight (kg) (mean ± SD) 63.26 ± 9.23 65.38 ± 10.47 0.89
BISAP score > 2 Before admission 9 (37.5%) 6 (26.08%) 0.74
Hematocrit (%) (mean ± SD) before admission 43.65 ± 5.56 40.38 ± 5.05 0.06
at 24 h 37 ± 5.39 36.51 ± 3.67 0.73
BUN (mg/dL) (mean ± SD) before admission 14.37 ± 5.96 13.4 ± 6.66 0.60
at 8e12 h 10.11 ± 2.42 10.53 ± 3.21 0.49
at 16e20 h 8.83 ± 3.12 8.19 ± 4.02 0.55

BISAP, bedside index of severity in acute pancreatitis (each point: BUN > 25 mg/dL, impaired consciousness, systemic inflammatory response syndrome, age > 60 and pleural
effusion); hr, hours; kg, kilograms; LRS, Lactated Ringer's solution; NSS, normal saline solution; SD, standard deviation.

Please cite this article in press as: Choosakul S, et al., Comparison of normal saline versus Lactated Ringer's solution for fluid resuscitation in
patients with mild acute pancreatitis, A randomized controlled trial, Pancreatology (2018), https://doi.org/10.1016/j.pan.2018.04.016
4 S. Choosakul et al. / Pancreatology xxx (2018) 1e6

Table 2
Effect of the type of fluid resuscitation on SIRS.

NSS (n ¼ 24) LRS (n ¼ 23) Risk difference (95% confidence interval) Risk ratio (95% confidence interval) P-value

SIRS score before resuscitation (median) (IQR) 1 (0, 2) 1 (0, 2) 0.54

SIRS score before resuscitation (n) (%) 0.91
0 7 (29.2%) 8 (34.8%)
1 7 (29.2%) 7 (30.4%)
2 5 (20.8%) 5 (21.7%)
3 5 (20.8%) 3 (13%)
4 0 0
SIRS before resuscitation 10 (41.7%) 8 (34.8%) e e 0.846
(SIRS score  2) (n) (%)
SIRS at 24 h (n) (%) 9 (37.5%) 2 (8.7%) 40.2 (12.2, 68.1) 1.96 (1.22, 3.16) 0.02
SIRS at 48 h (n) (%) 2 (8.3%) 2 (8.7%) 1.2 (52.4, 50.1) 0.98 (0.35, 2.72) 1
D SIRS at 24 ha 4.2% 26.1% e e 0.02
D SIRS at 48 hb 33.4% 26.1% e e 0.88

IQR, interquartile range; LRS, Lactated Ringer's solution; NSS, normal saline solution; SIRS, systemic inflammatory response syndrome.
a
D SIRS at 24 h is difference of SIRS at 24 h when compared with before resuscitation.
b
D SIRS at 24 h is difference of SIRS at 48 h when compared with before resuscitation.

Table 3
Effect of the type of fluid resuscitation on bio-inflammatory markers.

NSS (n ¼ 24) LRS (n ¼ 23) P-value

CRP at admission (median, mg/L) (IQR) 43.14 (7.59, 160.15) 31.11 (10.85, 153.82) 0.865
CRP change at 48 h (median, mg/L) (IQR) þ31.73 (1.97,27.2) þ18.19 (4.43,7.83) 0.756
ESR at admission (median, mm/h) (IQR) 28.5 (12.5, 46.5) 31 (15, 67) 0.694
ESR change at 48 h (median, mm/h) (IQR) þ14.5 (9.5, 30) þ28 (17, 21) 0.255
Procalcitonin at admission (median, ng/mL) (IQR) 0.19 (0.08, 0.47) 0.13 (0.08, 5.44) 0.915
Procalcitonin change at 48 h (median, ng/mL) (IQR) þ0.04 (0.02, 0.24) þ0.05 (0.01, 2.54) 0.171

CRP, C-reactive protein; ESR, erythrocyte sedimentary rate; IQR, interquartile range; LRS, lactate ringer's solution; NSS, normal saline solution.

Table 4
Clinical outcomes and mortality according to type of fluid therapy.

NSS (n ¼ 24) LRS (n ¼ 23) P-value

Total volume of fluid (mL) (mean ± SD) 5374.17 ± 768.82 4929.57 ± 1265.6 0.156
Length of stay (median, days) (IQR) 5.5 (4, 9) 6 (4, 9) 0.915
Local complication (n) (%) 9 (37.5%) 6 (26.08%) 0.74
Pancreatic necrosis 2 (8.3%) 0 (0%) 0.489
Acute peripancreatic fluid collection 6 (25%) 5 (21.7%) 0.792
Pseudocyst 0 (0%) 1 (4.3%) 0.489
Walled-off necrosis 1 (4.2%) 0 (0%) 1
Organ failure at 48 h (n) (%)
Shock 1 (4.2%) 0 (0%) 1
PaO2/FiO2 ratioa < 300 1 (4.2%) 1 (4.3%) 1
Creatinine > 1.9 mg/dl 1 (4.2%) 0 (0%) 1
In-hospital mortality (n) (%) 1 (4.2%) 0 (0%) 1
30-day mortality (n) (%) 1 (4.2%) 0 (0%) 1

IQR, interquartile range; LRS, Lactated Ringer's solution; NSS, normal saline solution; SD, standard deviation.
a
PaO2/FiO2 ratio is the ratio of arterial oxygen partial pressure to fractional inspired oxygen.

during admission. He was diagnosed with severe alcoholic hepatitis
and severe pancreatitis. Eventually, he developed infected walled-
of necrosis and underwent endoscopic necrosectomy. Unfortu-
nately, he died from multiple organ failure. No one else had surgery.
No patient from the LRS group died within 30 days. Nobody in our
study saw modifications in the protocol of fluid resuscitation by the
safety monitoring committee.
4. Discussion
The optimal fluid therapy for the treatment of acute pancreatitis
is still arguable. The administered solutions should not only
improve hemodynamic parameters, but should also bring positive
effects on the microcirculation and metabolic effect. The types of
fluid, crystalloid and/or colloid, used in the early hours of acute
pancreatitis remain under debate.
NSS, when given in large volume, may affect the development of
metabolic acidosis while LRS does not. Many experimental studies
revealed that low pH may activate zymogens and adversely impact
acinar cells. Ultimately, it make patients more susceptible to injury,
thereby providing increase in severity of acute pancreatitis. For this
reason, LRS with its pH (normal range, 6e7.5) may potentially
produce the protective effects on tissue and improve the outcome
of acute pancreatitis treatment in animal models [10]. However,
Young et al. compared buffer crystalloid (components and pH
similar to LRS) with NSS in acute kidney injury patients who un-
dergone renal replacement therapy in intensive care unit and found
the same outcome between the two treatments [11].
Our findings show that LRS significantly reduced SIRS in the first
24 h as compared to NSS. But this effect did not persist at 48 h. Our
result was consistent with those of Wu et al. [7], showing that LRS
reduced SIRS at 24 h as compared to NSS. However, SIRS reduction

Please cite this article in press as: Choosakul S, et al., Comparison of normal saline versus Lactated Ringer's solution for fluid resuscitation in
patients with mild acute pancreatitis, A randomized controlled trial, Pancreatology (2018), https://doi.org/10.1016/j.pan.2018.04.016
 S. Choosakul et al. / Pancreatology xxx (2018) 1e6
was evaluated for only 24 h whereas we evaluated SIRS to 48 h.
Another study by de-Madaria et al. showed that LRS did not
significantly reduce SIRS at 24, 48 and 72 h when compared to NSS
[12]. These results could be due to the fact that the volume of fluid
resuscitation in the first day of the study by de-Madaria et al. was
only 2100e2400 mL while the study by Wu et al. and our subjects
received about 4400 and 5156 mL in the first day. So, SIRS from
acute pancreatitis appears not only to depend on the type of fluid
resuscitation but also on the volume of fluid resuscitation.
These results correlate with the previous studies which showed
that aggressive fluid resuscitation is the cornerstone of manage-
ment of acute pancreatitis [13,14]. Nevertheless, some studies
suggested that aggressive hydration may be associated with
increased morbidity and mortality [15,16]. With our results, We
suggest aggressive fluid therapy for resuscitation in acute pancre-
atitis. However, the amount of the fluid should coincide with the
BUN level as a target for goal-directed therapy.
Our results showed that administration of LRS and NSS
increased the level of bio-inflammatory marker (CRP, procalcitonin
and ESR) at 48 h which was different from the study of Wu et al. and
de-Madaria et al. Study by Wu et al. showed that LRS could
significantly reduce level of CRP at 24 h while a study by de-
Madaria et al. showed that LRS could reduce CRP levels at 48 and
72 h as compared to NSS. This means CRP is not a good inflam-
matory marker because it does not follow SIRS. Our results which
showed an increase of bio-inflammatory marker (CRP, procalcito-
nin and ESR) at 48 h after admission correspond with other studies
that also showed higher level of bio-inflammatory marker in 48 and
72 h after the first admission date [17,18].
Our study showed that mortality was not difference between
NSS and LRS administration which was similar to the prospective
studies of Wu et al. [7] and de-Madaria et al. [12] and also similar to
the retrospective study of Lipinski et al. [19]. These results could be
due to most of the patients of those studies and our study were
mild acute pancreatitis. While study of Aboelsoud et al. [20]
showed that hospital mortality was significantly lower in LRS group
when compared to NSS group. This result could be due to they
included only severe cases of acute pancreatitis that have high
mortality in their study while most cases of our study were mild
pancreatitis that have low mortality. Another reason may be due to
the study by Aboesoud et al. has a large sample size than our study.
The mean total volume of fluid in our study was 5156 mL in the
first 24 h, while the median volume in Wu et al. was 4400 mL7. The
volume in this study was higher than in previous studies because
some physicians continued aggressive fluid for 2e4 h after check-
point 1 (8 h after admission) and checkpoint 2 (16 h after admis-
sion) even though patients were classed as fluid responsive.
Our study had several strengths. First, our study evaluated not
only SIRS reduction at first 24 h, but also SIRS reduction at 48 h. SIRS
reduction at 48 h was chosen because it was strongly associated
with increase in local complication, organ failure, and mortality
when compared with SIRS at 24 h [21]. Second, we have high safety
standard for enrolled patients in this study. Our research used
distinctive protocols in patients monitoring and fluid resuscitation
according to goal-directed therapy. Previous studies have shown
that excessive volume resuscitation especially in patients with
hemodilution, hematocrit <35% at 48 h after admission, had
increased incidence of sepsis and decreased survival rates [16]. Last,
this study is the largest study to date comparing two different types
of fluids for resuscitation in acute pancreatitis.
Despite that, there were several limitations to this study. First,
the major limitation of this study is its small sample size. Primary
outcome measure in this study was SIRS reduction but the pro-
portion of patients with SIRS at baseline in our study was 34-40%
which was lower than 60% in other studies [12,21]. If the sample
Please cite this article in press as: Choosakul S, et al., Comparison of normal saline versus Lactated Ringer's solution for fluid resuscitation in
patients with mild acute pancreatitis, A randomized controlled trial, Pancreatology (2018), https://doi.org/10.1016/j.pan.2018.04.016
5
size were larger, the primary endpoint might have been different.
Nevertheless, some studies also reported SIRS at baseline were 20-
35% [22,23] which were similar to our study. Second, the assump-
tion for the sample size calculation was 0% improvement in SIRS
with NSS. It was unusual to assume that none of the patients
receiving NSS would have improvement in SIRS. Some patients may
in fact improve even without fluids due to the natural course of the
disease. Nevertheless, when we planned to start our study, there
was only one prospective study by Wu et al [7] which showed that
SIRS reduction was 0% in NSS group. Third, we only enrolled the
patients from the emergency department, so our results did not
take into account acute pancreatitis from post-ERCP. Having said
that, this should have little impact on our results as there are very
low incidence of post- ERCP pancreatitis in Phramongkutklao
hospital. This is because universal use of rectal indomethacin for
prophylaxis post-ERCP pancreatitis at the hospital. Forth, we used
strict inclusion criteria, thus we also excluded the patients with
major co-morbid disease. The results from this study cannot be
applied to some patients who have major co-morbid disease.
However, patients with severe co-morbid disease generally would
have contraindication for aggressive volume resuscitation and need
close monitoring such as invasive hemodynamic monitoring which
means we would not be able to follow goal directed therapy pro-
tocol. Last, alcohol is the second common etiology of acute
pancreatitis. So some alcoholic pancreatitis also have liver disease.
LRS has limitations in patients with liver disease, because lactate is
metabolized into bicarbonate by the liver. Further investigation on
the effect of acetar for fluid resuscitation in AP (TCTR20170903001),
should be conducted in the future as acetar is metabolized into
bicarbonate by the muscle and so it can use in patients with liver
disease.
5. Conclusion
Lactated Ringer's solution was safe in acute pancreatitis. It was
superior to NSS in SIRS reduction only in the first 24 h. However,
SIRS at 48 h and mortality were not different between LRS and NSS.
Additional studies are recommended to provide further data on
amount and type of resuscitation fluid most useful for patients with
acute pancreatitis.
Grant support
The present study was supported by a grant from The Gastro-
enterological Association of Thailand.
Disclosures
“No competing interests declared for either author”.
Author contributions
SC. Study management, research implementation, data analysis
and interpretation, drafting the article.
KH, SK, KO, TS and WP were vital as implementers, data col-
lectors, data interpretation and manuscript revising.
CP. Study design, data interpretation and final approval of the
version.
All authors: Final approval of the version to be published.
Acknowledgements
The author would like to express sincere gratitude to all
gastroenterology and research nurses and the patients in this study.
Our sincere thanks also goes to Dr. Sujiphong Davis for giving
6 S. Choosakul et al. / Pancreatology xxx (2018) 1e6

suggestions about the manuscript. This study was supported by the
Gastroenterological Association of Thailand. Our preliminary anal-
ysis were presented as an oral lecture at Digestive Disease Week
(DDW), Chicago, Illinois, USA, on May 7, 2017.
The present study was supported by a grant from The Gastro-
enterological Association of Thailand. No competing interests
declared for either author.
Appendix A. Supplementary data
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.pan.2018.04.016.
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Please cite this article in press as: Choosakul S, et al., Comparison of normal saline versus Lactated Ringer's solution for fluid resuscitation in
patients with mild acute pancreatitis, A randomized controlled trial, Pancreatology (2018), https://doi.org/10.1016/j.pan.2018.04.016