Ringer’s Lactate vs Normal Saline in Acute Pancreatitis: A Systematic Review and meta-

analysis
Type of study: Review (systematic review and meta-analysis)

First and Corresponding Author: Umair Iqbal, MD

PGY-III Internal Medicine Resident
Bassett medical Center
Accepted Article
Address: One Atwell Road, Cooperstown NY 13326
Contact no. 6072822759, umairiqbal_dmc@hotmail.com

Second Author: Hafsa Anwar, MBBS

Jinnah Sindh Medical University
Contact info: 6072826105, hafsaanwar93@gmail.com

Third author: Melissa Scribani, MPH

Bassett Medical Center
Contact info: 6075473456, mbrower@gmail.com

Conflict of Interest: we do not have any conflict of interest

Funding: None
Grant Support: None
Acknowledgments: None

ABSTRACT
Introduction: Acute Pancreatitis (AP) is one of the most common causes of hospitalization in
the United States. Aggressive intravenous hydration with crystalloids is the first step in
management, and is associated with improved survival. Guidelines are unclear regarding the
choice of crystalloids. Normal saline (NS) is most commonly used, but recent studies have
shown Ringer’s lactate (RL) to be associated with better outcomes.
Methods: A comprehensive literature review was conducted by searching the Embase,

This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which
may lead to differences between this version and the Version of Record. Please cite this
article as doi: 10.1111/cdd.12606

This article is protected by copyright. All rights reserved.

 MEDLINE, Pubmed, and Google Scholar databases through December 2017 to identify all
studies that compared the use of NS with RL for the management of acute pancreatitis. Two
independent reviewers extracted data and assessed the quality of publications; a third investigator
resolved any discrepancies.
Accepted Article
Results: Five studies, three randomized controlled trials and two retrospective cohort studies,
including 428 patients, were included in this analysis. Mortality trended lower in the RL group,
but was not statistically significant (pooled odds ratio 0.61 (0.28-1.29; P=0.20)). Patients in the
RL group had significantly decreased odds of developing systemic inflammatory response
(SIRS) at 24 hours (pooled odds ratio 0.38 (0.15-0.98; P=0.05)).
Conclusion: This study demonstrated that RL has anti-inflammatory effects and is associated
with decreased odds of persistent SIRS at 24 hours, which is a marker of severe disease in
patients with AP. Although mortality trended lower in RL group, it did not achieve statistical
significance and hence larger randomized controlled trials are needed to evaluate this
association.
Keywords: Ringer’s lactate; normal saline; acute pancreatitis; Systemic inflammatory response
syndrome; SIRS; pancreatic necrosis

Introduction:
Acute pancreatitis (AP) is an inflammatory disorder of the pancreas characterized by abdominal
pain, nausea and vomiting. It is the most common cause of hospitalization among gastrointestinal
diseases in the United States [1]. Common etiologies of AP include gallstones, alcohol use,
hypertriglyceridemia and certain medications [2-4]. Overall mortality in patients hospitalized
with AP is approximately 10%, but it is as high as 30% in severe necrotizing pancreatitis [5,6].
Mortality in the acute phase is mostly related to SIRS (systemic inflammatory response) and

This article is protected by copyright. All rights reserved.

 organ failure [7]. It is therefore important to prevent systemic inflammatory response to decrease
mortality and morbidity with this disease.
Aggressive intravenous hydration is the first step in managing AP and is associated with
improved survival [6,8]. Crystalloids are usually preferred for treatment, and normal saline (NS)
Accepted Article
is the most commonly used as an initial fluid for intravenous hydration in these patients [9].
Recent studies have shown that use of a more balanced solution, Ringer’s lactate (RL), can
improve mortality rates and decrease development of SIRS over 24-48 hours in these patients
when compared to normal saline [10-14]. However, existing data is conflicting and limited to
small studies. We therefore performed a systematic review and meta-analysis to delineate
whether choice of fluid in managing pancreatitis has any association with patient outcomes,
namely mortality, SIRS, and pancreatic necrosis.

Methods:
Information sources and Search Strategy:
A systematic literature search was conducted using the Pubmed, Embase, MEDLINE and Google
Scholar databases from inception to December 2017 to identify all original studies that
investigated the comparison of Ringer’s lactate with normal saline in acute pancreatitis. The
systematic literature review was independently conducted by two investigators (U.I, H.A) using
a search strategy that included the terms for “Acute Pancreatitis,” “Normal Saline,” “sodium
chloride,” and “Ringer’s lactate.” A manual search for further relevant articles was also
performed using references of the included articles. We did not apply any language limitation
for the inclusion of studies. Our study was conducted in agreement with the Preferred Reporting
Items for Systematic Reviews and Meta-Analysis (PRISMA) statement which is provided as
Online Supplementary Data 1 [15].
Selection criteria
Eligible studies were required to be randomized controlled trials (RCTs), cross-sectional, or
cohort studies that had investigated the comparison of use of normal saline and Ringer’s lactate
in acute pancreatitis. We excluded studies among patients with post-ERCP pancreatitis or
diseases other than AP. Studies were required to provide the effect estimates (odds ratios (ORs),
relative risks (RRs), hazard ratios (HRs) or standardized incidence ratio (SIR)) with 95%
confidence intervals (CIs) or sufficient raw data to calculate it. Study size did not restrict the

This article is protected by copyright. All rights reserved.

 inclusion of studies.

Quality assessment
Newcastle-Ottawa quality assessment scale was used to evaluate the quality of cohort study in
Accepted Article
three areas, including the recruitment of cases and controls, the comparability between the two
groups and the ascertainment of the outcome of interest for cohort study. Methodological quality
of randomized trials included for the analysis was measured using the Jadad scoring system from
0 to 5 [16]. Results of methodological quality assessment did not influence the eligibility of the
studies.

Data abstraction
A organized data collection form was used to abstract the following data from each study: title of
the study, publication year, name of the first author, year of the study, country where the study
was performed, number of participants, demographic data of participants, type of fluid use,
outcome measurement (outcomes included mortality, development of SIRS criteria on admission
and at 24 hours, and pancreatic necrosis). To ensure accuracy, this data abstraction process was
independently done by two investigators (UI and HA) and was reviewed by the third investigator
(MS).

Statistical Analysis:
Data analysis was performed using Review Manager (RevMan) 5.3 software from the Cochrane
Collaboration (London, UK). For the main outcome (mortality), the effect of RL compared with
NS was determined using the Mantel-Haenszel odds ratio (OR). When considering this outcome,
an overall OR of less than one indicated that the odds of death were lower in the treatment group
than the odds of death in the control group. A fixed-effects model was utilized for this meta-
analysis, with point estimates, variance, and weights for each study based on the size of the study
and the number of events. Heterogeneity was assessed using the I2 index. A value of I2 of 0–25%
represented insignificant heterogeneity, 26–50% represented low heterogeneity, 51–75%
represented moderate heterogeneity, and >75% represented high heterogeneity [17].
The secondary outcomes of presence of SIRS at 24 hours post-treatment as well as presence of
pancreatic necrosis were analyzed in the same fashion.

This article is protected by copyright. All rights reserved.

 Publication bias:
A funnel plot of effect size against sample size was produced for the studies included in the
meta-analysis to evaluate for the presence of any publication bias.
Accepted Article
Results:
Four thousand three hundred and thirty five potentially eligible articles were identified using our
search strategy. After exclusion of duplicates, 2647 studies underwent title and abstract review.
2623 were excluded at this stage since they were case reports, correspondence, review articles, or
studies done in patients other than AP leaving 24 articles for full-text review. Nineteen of those
were excluded after the full-length review as they did not report the outcome of interest or were
not done in patients with AP. Among those 19 excluded studies, a majority reported comparison
of RL with NS in post ERCP pancreatitis. Therefore, 5 studies with 428 participants met the
eligibility criteria. Two of the included studies were retrospective observational cohort studies
and three were RCTs. One of the RCTs was presented as an abstract only and was not yet fully
published. Manual review of the included studies and some selected review articles did not yield
additional eligible studies. The literature search, review, and selection process are shown in
(Figure 1). Baseline characteristics of included studies are shown in (Table 1).
Out of 428 included patients, 259 received normal saline infusion and 169 received Ringer’s
lactate.
Mortality:
The overall mortality rate for included studies was 8.2% (35/428). Nine patients died in the RL
group and 26 patients died in the NS group. Hence, patients in RL group had decreased odds of
mortality using the pooled odds ratio (OR= 0.61 (0.28-1.29; P=0.20)). Although mortality
trended lower in the RL group it did not reach statistical significance (Figure 2).
Systemic Inflammatory Response Syndrome (SIRS):
Only three studies including 127 patients reported SIRS criteria in patients on admission and at
24 hours. 23 patients in the RL group and 28 in the normal saline group met SIRS criteria on
admission (Table 2). After 24 hours, only 9 patients in the RL group met SIRS criteria compared
to 26 in the NS group. Thus, patients in the RL group had decreased odds of meeting SIRS
criteria at 24 hours compared to NS (pooled odds ratio= 0.38 (0.15-0.98; P=0.05)). (Figure 3)
Pancreatic necrosis:

This article is protected by copyright. All rights reserved.

 Three studies including 183 patients reported development of pancreatic necrosis. Pancreatic
necrosis developed in 14 patients in the RL group compared to 23 patients in the NS group. No
statistically significant difference in the odds of pancreatic necrosis was observed between the
two groups (p=0.54).
Accepted Article
Heterogeneity among studies was low as seen by the I2 of 46% for the mortality outcome, and
I2=36% for SIRS at 24 hours. There was no publication bias as seen by the funnel plot diagram
(Figure 4).

Discussion:
To the best of our knowledge and based on our literature search, this is the first systematic
review and meta-analysis which summarizes all the current evidence available that compares the
use of RL and NS in management of AP. As stated earlier, development of SIRS in patients with
AP is the major predictor of mortality. Persistence of SIRS in AP results in reduction of end-
organ perfusion and may lead to subsequent third spacing of fluids. A study done on 252 patients
with AP revealed the presence of SIRS on day 1 and its persistence was associated with
increased risk for severe disease [7]. Similar results were seen in a study done on 759 patients
and revealed persistent SIRS to be associated with increased mortality and multiorgan
dysfunction [18]. de-Madaria et al. showed RL to be associated with decreased persistence of
SIRS, and similar results were also shown in a study done by Wu et al which supports the anti-
inflammatory effects of RL [12,13]. CRP is a cost-effective, widely used non-specific
inflammatory marker and multiple studies have shown it to be a useful predictor of severity of
AP [19-22]. Wu et al. and de-Madaria have shown in their studies that patients in RL groups
have significantly lower CRP levels at 24-48 hours compared to NS groups [12,13]. These
findings further point to the anti-inflammatory effects of Ringer’s lactate in patients with AP.
This anti-inflammatory effect of RL due to decreased persistence of SIRS has two possible
explanations. First, RL has a slightly higher pH compared to NS (RL pH=6.5 versus NS
pH=5.5). Studies show that acidosis enhances inflammation and necrosis in AP [23,24].
Extracellular acidosis signals the release of inflammatory cytokines IL-1β in immune cells [25].
Lactate in RL is metabolized in the liver, which results in lower metabolic acidosis and hence
protective effects which decrease the development of SIRS in patients with AP. Second, RL may
directly decrease inflammatory response in these patients [12]. In a study done on THP-1

This article is protected by copyright. All rights reserved.

 inflammatory cells, the presence of RL in-vitro prevents activation of NF-KB, the transcription
factor involved in the inflammatory process. This inhibition is secondary to the effect of lactate,
as use of Ringer’s alone without lactate results in the loss of this inhibition [12]. This beneficial
anti-inflammatory effect of lactate has also been shown in experimental models [26,27].
Accepted Article
Arterial pH, base deficit and bicarbonate levels have shown to be useful markers in predicting
the severity of pancreatitis [28]. Normal saline is the most widely used crystalloid worldwide [9].
Large amounts of NS can cause elevated chloride and decrease serum bicarbonate levels and
hence cause hyperchloremic metabolic acidosis, which is associated with acute kidney injury and
poor outcomes [29-33]. This effect has been shown in large volume resuscitation in trauma
patients resulting in hyperchloremia and non-anion gap metabolic acidosis [34,35]. Animal
models also shown that volume resuscitation in hemorrhagic shock with NS is associated with
poor outcomes secondary to metabolic acidosis, hyperkalemia and vasodilation, and suggested
the use of RL to be superior to NS [36,37]. NS has also been shown to be associated with poor
outcomes in critically ill septic patients secondary to its potential for hyperchloremia, which is an
independent predictor of all-cause mortality in these patients [29]. In a recently published
randomized controlled trial done on 7942 critically ill patients revealed balanced
crystalloids are associated with less mortality, need for renal replacement therapy or
persistent renal dysfunction compared to saline infusion [30]. The mortality benefit was
only significant in critically ill patients, as another randomized controlled trial revealed no
difference in mortality in non-critically ill patients but the risk of major adverse kidney
events were again significantly lower in balance crystalloids group compared to patients
who receive saline [31].
RL has also been shown to be beneficial in the prevention of post ERCP pancreatitis (PEP).
RCTs have shown prophylactic and post-procedural aggressive fluid hydration with RL
decreases the incidence and severity of PEP [38-40]. In a randomized trial including 62 patients,
patients who received aggressive hydration (3 cc/kg/hr) were less likely to develop PEP
compared to those who received standard hydration with RL (1.5 cc/kg/hr) [38]. Similar results
were seen by subsequent studies and found aggressive hydration with RL to be beneficial in
preventing PEP [40]. Hence, the American Society of Gastrointestinal Endoscopy recommends
aggressive periprocedural RL for decreasing the incidence of PEP [41].
The systematic literature review process of this study was comprehensive, and the quality of

This article is protected by copyright. All rights reserved.

 included studies was fair to good, although one of the included studies was an abstract and not
yet fully published [14]. Moreover, the statistical heterogeneity of this meta-analysis was
relatively low and there was no publication bias. We acknowledge, however, that this study had
some limitations and, thus, the results should be interpreted with caution. Firstly, the definition
Accepted Article
of mortality was not clear from some of the included studies. Specifically, the cause of death and
the time between exposures to Ringer’s lactate/normal saline until death was not reported
consistently across studies. Secondly, although our review includes three RCTs with fair quality,
their sample sizes were modest, and hence there is a need for larger RCTs to further support and
delineate the anti-inflammatory and survival benefit of RL in patients with AP.

Conclusion:
Current treatment guidelines for acute pancreatitis recommend aggressive intravenous hydration,
but do not comment on the efficacy of different types of fluids in decreasing mortality and
complications. Decrease odds of persistent SIRS using RL may be related to its potential
anti-inflammatory effects.
Mortality also trended lower in RL patients, but was not statistically significant. Larger
randomized controlled trials are necessary to further strengthen the association of RL with
favorable outcomes in patients with AP, however, our findings may help clinicians in making
decisions regarding the choice of fluid for management of AP.

References:
1. Peery AF, Crockett SD, Barritt AS, Dellon ES, Eluri S, Gangarosa LM, et al. Burden of
Gastrointestinal, Liver, and Pancreatic Diseases in the United States. Gastroenterology.
2015 Dec;149(7):1731–1741.e3.
2. Yang AL, Vadhavkar S, Singh G, Omary MB. Epidemiology of alcohol-related liver and
pancreatic disease in the United States. Arch Intern Med. 2008 Mar 24;168(6):649–56.
3. Toskes PP. Hyperlipidemic pancreatitis. Gastroenterol Clin North Am 1990;19(4):783–91.
4. Sarles H. Revised classification of pancreatitis--Marseille 1984. Dig Dis Sci. 1985
Jun;30(6):573–4.
5. Forsmark CE, Baillie J, AGA Institute Clinical Practice and Economics Committee, AGA
Institute Governing Board. AGA Institute technical review on acute pancreatitis.
Gastroenterology. 2007 May;132(5):2022–44.
6. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines
for the management of acute pancreatitis. Pancreatology. 2013 Aug;13(4 Suppl 2):e1-15.
7. Singh VK, Wu BU, Bollen TL, Repas K, Maurer R, Mortele KJ, et al. Early systemic
inflammatory response syndrome is associated with severe acute pancreatitis. Clin Gastroenterol
Hepatol. 2009 Nov;7(11):1247–51.

This article is protected by copyright. All rights reserved.

 8. Tenner S, Baillie J, DeWitt J, Vege SS, American College of Gastroenterology. American
College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol.
2013 Sep;108(9):1400–1415; 1416.
9. Myburgh JA. Fluid resuscitation in acute medicine: what is the current situation? J Intern Med.
2015 Jan;277(1):58–68.
10. Aboelsoud MM, Siddique O, Morales A, Seol Y, Al-Qadi MO. Fluid Choice Matters in
Accepted Article
Critically-ill Patients with Acute Pancreatitis: Lactated Ringer’s vs. Isotonic Saline. R I Med J
(2013). 2016 Oct 4;99(10):39–42.
11. Lipinski M, Rydzewska-Rosolowska A, Rydzewski A, Rydzewska G. Fluid resuscitation in
acute pancreatitis: Normal saline or lactated Ringer’s solution? World J Gastroenterol. 2015 Aug
21;21(31):9367–72.
12. Enrique de-Madaria, Iván Herrera-Marante, Verónica González-Camacho, Laia Bonjoch,
Noé Quesada-Vázquez, Isabel Almenta-Saavedra, et al. Fluid resuscitation with lactated Ringer’s
solution vs normal saline in acute pancreatitis: A triple-blind, randomized, controlled trial.
United European Gastroenterology Journal. 2017 Apr 27;2050640617707864.
13. Wu BU, Hwang JQ, Gardner TH, Repas K, Delee R, Yu S, et al. Lactated Ringer’s solution
reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin
Gastroenterol Hepatol. 2011 Aug;9(8):710–717.e1.
14. Choosakul S, Harinwan K, Chirapongsathorn S, Puttapitakpong C. Comparison of Normal
Saline Versus Lactated Ringer’s Solution for Fluid Resuscitation in Patients with Acute
Pancreatitis, A Randomized Controlled Trial. Gastroenterology. 152(5):S72.
15. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for
systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009 Aug
18;151(4):264–9, W64.
16. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing
the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials.
1996 Feb;17(1):1–12.
17. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-
analyses. BMJ. 2003 Sep 6;327(7414):557–60.
18. Mofidi R, Duff MD, Wigmore SJ, Madhavan KK, Garden OJ, Parks RW. Association
between early systemic inflammatory response, severity of multiorgan dysfunction and death in
acute pancreatitis. Br J Surg. 2006 Jun;93(6):738–44.
19. Leese T, Shaw D, Holliday M. Prognostic markers in acute pancreatitis: can pancreatic
necrosis be predicted? Ann R Coll Surg Engl. 1988 Jul;70(4):227–32.
20. Wilson C, Heads A, Shenkin A, Imrie CW. C-reactive protein, antiproteases and complement
factors as objective markers of severity in acute pancreatitis. Br J Surg. 1989 Feb;76(2):177–81.
21. Büchler M, Malfertheiner P, Schoetensack C, Uhl W, Beger HG. Sensitivity of antiproteases,
complement factors and C-reactive protein in detecting pancreatic necrosis. Results of a
prospective clinical study. Int J Pancreatol. 1986 Oct;1(3–4):227–35.
22. Mayer AD, McMahon MJ, Bowen M, Cooper EH. C reactive protein: an aid to assessment
and monitoring of acute pancreatitis. J Clin Pathol. 1984 Feb;37(2):207–11.
23. Noble MD, Romac J, Vigna SR, Liddle RA. A pH-sensitive, neurogenic pathway mediates
disease severity in a model of post-ERCP pancreatitis. Gut. 2008 Nov;57(11):1566–71.
24. Bhoomagoud M, Jung T, Atladottir J, Kolodecik TR, Shugrue C, Chaudhuri A, et al.
Reducing extracellular pH sensitizes the acinar cell to secretagogue-induced pancreatitis
responses in rats. Gastroenterology. 2009 Sep;137(3):1083–92.

This article is protected by copyright. All rights reserved.

 25. Rajamäki K, Nordström T, Nurmi K, Åkerman KEO, Kovanen PT, Öörni K, et al.
Extracellular acidosis is a novel danger signal alerting innate immunity via the NLRP3
inflammasome. J Biol Chem. 2013 May 10;288(19):13410–9.
26. Hoque R, Farooq A, Ghani A, Gorelick F, Mehal WZ. Lactate reduces liver and pancreatic
injury in Toll-like receptor- and inflammasome-mediated inflammation via GPR81-mediated
suppression of innate immunity. Gastroenterology. 2014 Jun;146(7):1763–74.
Accepted Article
27. Kellum JA, Song M, Li J. Lactic and hydrochloric acids induce different patterns of
inflammatory response in LPS-stimulated RAW 264.7 cells. Am J Physiol Regul Integr Comp
Physiol. 2004 Apr;286(4):R686-692.
28. Sharma V, Shanti Devi T, Sharma R, Chhabra P, Gupta R, Rana SS, et al. Arterial pH,
bicarbonate levels and base deficit at presentation as markers of predicting mortality in acute
pancreatitis: a single-centre prospective study. Gastroenterol Rep (Oxf). 2014 Aug;2(3):226–31.
29. Neyra JA, Canepa-Escaro F, Li X, Manllo J, Adams-Huet B, Yee J, et al. Association of
Hyperchloremia With Hospital Mortality in Critically Ill Septic Patients. Crit Care Med. 2015
Sep;43(9):1938–44.
30. Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, et al.
Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018
01;378(9):829–39.
31. Self WH, Semler MW, Wanderer JP, Wang L, Byrne DW, Collins SP, et al. Balanced
Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med. 2018 01;378(9):819–28.
32. Kellum JA. Saline-induced hyperchloremic metabolic acidosis. Crit Care Med. 2002
Jan;30(1):259–61.
33. Young JB, Utter GH, Schermer CR, Galante JM, Phan HH, Yang Y, et al. Saline versus
Plasma-Lyte A in initial resuscitation of trauma patients: a randomized trial. Ann Surg. 2014
Feb;259(2):255–62.
34. Barker ME. 0.9% saline induced hyperchloremic acidosis. J Trauma Nurs. 2015
Apr;22(2):111–6.
35. Ho AM, Karmakar MK, Contardi LH, Ng SS, Hewson JR. Excessive use of normal saline in
managing traumatized patients in shock: a preventable contributor to acidosis. J Trauma. 2001
Jul;51(1):173–7.
36. Martini WZ, Cortez DS, Dubick MA. Comparisons of normal saline and lactated Ringer’s
resuscitation on hemodynamics, metabolic responses, and coagulation in pigs after severe
hemorrhagic shock. Scand J Trauma Resusc Emerg Med. 2013 Dec 11;21:86.
37. Todd SR, Malinoski D, Muller PJ, Schreiber MA. Lactated Ringer’s is superior to normal
saline in the resuscitation of uncontrolled hemorrhagic shock. J Trauma. 2007 Mar;62(3):636–9.
38. Buxbaum J, Yan A, Yeh K, Lane C, Nguyen N, Laine L. Aggressive hydration with lactated
Ringer’s solution reduces pancreatitis after endoscopic retrograde cholangiopancreatography.
Clin Gastroenterol Hepatol. 2014 Feb;12(2):303–307.e1.
39. Choi J-H, Kim HJ, Lee BU, Kim TH, Song IH. Vigorous Periprocedural Hydration With
Lactated Ringer’s Solution Reduces the Risk of Pancreatitis After Retrograde
Cholangiopancreatography in Hospitalized Patients. Clin Gastroenterol Hepatol 2017; 15: 86–
92.e1.
40. Shaygan-Nejad A, Masjedizadeh AR, Ghavidel A, Ghojazadeh M, Khoshbaten M.
Aggressive hydration with Lactated Ringer’s solution as the prophylactic intervention for
postendoscopic retrograde cholangiopancreatography pancreatitis: A randomized controlled
double-blind clinical trial. J Res Med Sci. 2015 Sep;20(9):838–43.

This article is protected by copyright. All rights reserved.

 41. ASGE Standards of Practice Committee, Chandrasekhara V, Khashab MA, Muthusamy VR,
Acosta RD, Agrawal D, et al. Adverse events associated with ERCP. Gastrointest Endosc. 2017
Jan;85(1):32–47.
Accepted Article

This article is protected by copyright. All rights reserved.

 Figure 1: Literature review proccess
Accepted Article

This article is protected by copyright. All rights reserved.

 Figure 2:
2 Forest Plott of all inclu
uded studies for mortalityy
Accepted Article

This article is protected by copyright. All rights reserved.

 Figure 3: Forest Plott of studies for
f SIRS at 24 hours
Accepted Article

This article is protected by copyright. All rights reserved.

 Figure 4: Funnel plot diagram for publication bias
Accepted Article

This article is protected by copyright. All rights reserved.

Accepted Article

This article is protected by copyright. All rights reserved.

 Table 1: Baseline characteristics of included studies

First author, Aboelsoud et al. Lipinski et al de-Madaria et Wu et al. Choosakul et

Publication 2016 2015 al. 2017 2011 al.
Accepted Article
year, country 2017
Beth Isreal Central Clinical Alicante General 3 New England
Deaconess hospital of the Hospital, Spain Hospitals, USA NA
Medical Center, ministry of
Boston, interior Poland
MA,USA

Sample size N=198 N=103 N=40 N-40 N=47

Baseline Median Age Mean Age= 51.2 Mean Age Median Age NA
characteristics RL= 63 Males= 66% RL=63.8 RL=50
Saline=56 Saline=61.4 Saline=54
Males=50.5% Male=47.5% Male=55%
Severity of BISAP score ≥3 BISAP score ≥3 SIRS≥2 criteria Median BISAP SIRS at
disease RL= 22% RL= 20% RL=47.4% on enrollment admission
NS=35% NS=12.7% NS=66.7% RL=0 RL=34.8%
NS=1 NS=41.7%
Median CRP
levels Median
RL=3.4 APACHE II
NS=4.8 RL=3
NS=3

Design of the Retrospective Retrospective Triple blind Open label Open label
study cohort study cohort study randomized randomized randomized
controlled trial controlled trial controlled trial
Study MIMIC database All patient All patients >18 Patient admitted Patient with the
population was used to admitted to the years of age with acute diagnosis of
identify patients department of presented to the pancreatitis at 3 acute
admitted to ICU Gastroenterolog emergency New England pancreatitis
with acute y of the Central department of hospitals from
pancreatitis at Clinical hospital Alicante General May 2009-Feb
BIDMC between of the ministry University 2010.
2001-2012 of interior Hospital from
(Poland) with a Feb 2013- March
diagnosis of 2015 with first
acute episode of acute
pancreatitis pancreatitis
between 2011-
2012
New castle Selection= 3 Selection=3 JADAD score=5 JADAD score=3 JADAD score=
Ottawa Comparability=1 Comparability= 1
Quality Outcome=3 0 (study was not
assessment Outcome=3 yet published)

This article is protected by copyright. All rights reserved.

 scale or
JADAD score
Mortality, Mortality, Development of Development of SIRS at 24 and
Outcomes hospital stay, hospital stay, SIRS at 24, 48 SIRS at 24 48 hours,
changes in serum pancreatic and 72 hours. hours, mortality,
HCO3 levels necrosis Mortality, Mortality, Hospital Stay,
Hospital stay, Hospital stay, change in ESR,
Accepted Article
pancreatic changes in CRP, procalcitonin
necrosis BUN & and CRP
bicarbonate,

MIMIC= Multi-parameter Intelligent Monitoring in Intensive Care, BIDMC=Beth Israel Deaconess

Medical Center NCOQ= Newcastle Ottawa Quality, SIRS= Systemic inflammatory response syndrome,
HCO3= bicarbonate, CRP= C-reactive protein, ESR=Erythrocyte sedimentation rate, BUN= Blood urea
nitrogen, RL=Ringers lactate, BISAP score= Bedside index of severity in acute pancreatitis score,
APACHE II= Acute Physiology and Chronic Health Evaluation II

This article is protected by copyright. All rights reserved.

 Table 2: Patients meeting SIRS criteria on presentation and at 24 hours
Ringers lactate (N= 61 ) Normal Saline (N=66 P value
)
SIRS on presentation 23 28 0.58
SIRS at 24 hours 7 17 0.05
Accepted Article

This article is protected by copyright. All rights reserved.