REVIEW

CURRENT
OPINION Intravenous fluid resuscitation in the management
of acute pancreatitis
Jorge D. Machicado a and Georgios I. Papachristou b

Purpose of review
In the absence of proven effective pharmacologic therapy in acute pancreatitis, and given its simplicity,
wide availability, and perceived safety, intravenous fluid resuscitation remains the cornerstone in the early
treatment of acute pancreatitis. Herein, we will review the rationale of fluid therapy, critically appraise the
published literature, and summarize recent studies.
Recent findings
Several observational studies and small clinical trials have raised concern about the efficacy and safety of
aggressive fluid resuscitation. Early aggressive fluid therapy among acute pancreatitis patients with
Downloaded from http://journals.lww.com/co-gastroenterology by BhDMf5ePHKbH4TTImqenVOm0oSGVjfT8jCxH6smnuq6G3+01QLgP+EiY/vyMy1iF on 08/08/2020

predicted mild severity appears to have the highest benefit, whereas aggressive resuscitation in patients
with predicted severe disease might be futile and deleterious. Lactated Ringer’s solution is the preferred
fluid type based on animal studies, clinical trials, and meta-analyses. There is a wide variation of fluid
resuscitation approaches in current guideline recommendations, quality indicators, and worldwide practice
patterns.
Summary
There is lack of high-quality data that supports the use of early aggressive fluid resuscitation. Large, well
designed, multicenter randomized controlled trials are needed to determine the optimal timing, fluid type,
volume, rate, and duration of fluid resuscitation in acute pancreatitis.
Keywords
acute pancreatitis, fluid resuscitation, intravenous fluids, therapy

INTRODUCTION After initial pancreatic acinar injury, proinflamma-

Annually, approximately 2.5 million people
develop acute pancreatitis worldwide, and 100 000
die from the disease [1]. In the absence of proven
effective pharmacologic therapies in acute pancrea-
titis, and given its simplicity, wide availability, and
perceived safety, intravenous fluid resuscitation is
considered the mainstay in the early treatment of
&
acute pancreatitis [2 ]. In the last decade, several
studies have raised concerns about the efficacy and
safety of early aggressive fluid resuscitation in the
outcomes of acute pancreatitis. Thus, we will review
the rationale of this approach, critically appraise the
published literature, and summarize the results of
pivotal studies that shape our current understand-
ing of intravenous fluid resuscitation in acute pan-
creatitis.
RATIONALE OF FLUID THERAPY
The critical role of fluid resuscitation is based on the
alteration of the pancreatic microcirculation and
systemic hemodynamics during acute pancreatitis.
tory cytokines and vasoactive mediators increase
vascular permeability, interstitial fluid extravasa-
tion, capillary vasoconstriction, and microthrombi
formation [3–5]. All these phenomena impair the
pancreatic microcirculation, increase local ische-
mia, and can ultimately lead to pancreatic necrosis
[6]. As a result of third spacing and volume loss,
intravascular volume decreases, leading to tissue
hypoperfusion, which can then precipitate organ
failure and eventually death [7,8].
a
Division of Gastroenterology & Hepatology, Mayo Clinic Health System,
Eau Claire, Wisconsin and bDivision of Gastroenterology, Hepatology &
Nutrition, The Ohio State University Wexner Medical Center, Columbus,
Ohio, USA
Correspondence to Georgios I. Papachristou, MD, PhD, Professor of
Medicine, Division of Gastroenterology, Hepatology & Nutrition, The Ohio
State University Wexner Medical Center, 395 W. Twelfth Ave, Columbus,
OH 43210, USA. Tel: +1 614 506 2134;
e-mail: georgios.papachristou@osumc.edu
Curr Opin Gastroenterol 2020, 36:409–416
DOI:10.1097/MOG.0000000000000659

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Pancreas

consequences of hypoperfusion, several animal

KEY POINTS
 Aggressive intravenous fluid resuscitation appears to be
beneficial when started within the first 4 h from hospital
presentation in patients with predicted mild acute
pancreatitis and administered for duration of 12–24 h.
 Late onset of aggressive intravenous fluid resuscitation
beyond the therapeutic window of 4–6 h or in
predicted severe acute pancreatitis might be futile
and deleterious.
 Lactated Ringer’s solution is preferred over colloids or
other crystalloids, given its antiinflammatory effect in
animal studies, clinical trials, and meta-analyses.
 In the absence of conclusive high-quality data, there is
a wide variation of intravenous fluid resuscitation
approaches in current guideline recommendations,
quality indicators, and worldwide practice patterns.
 Large, well designed, multicenter randomized
controlled trials are required to clarify the role of early
aggressive fluid resuscitation and preferred fluid type in
acute pancreatitis, and to determine the precise
volume, rate, and duration of fluid therapy required.
studies emerged in the 1980s, showing that fluid
resuscitation improves pancreatic microcirculation,
systemic perfusion, and overall survival [9–13].
Therefore, even before clinical data was available,
intravenous fluid resuscitation was advocated to
mitigate the disease process [14].
Evidence supporting fluid resuscitation in
humans became available in the late 1990s. In a
single-center, case–control study comparing patients
with mild and necrotizing acute pancreatitis, hemo-
concentration and/or failure to decrease admission
hematocrit at 24 h were significantly associated with
development of pancreatic necrosis [15]. Further-
more, all patients with hemoconcentration and ris-
ing hematocrit at 24 h progressed to necrotizing
pancreatitis in a follow-up study from the same group
[16]. These studies supported hemoconcentration as
an early marker of impaired microcirculation and
pancreatic necrosis, suggesting that adequate fluid
resuscitation with decreasing hematocrit may pre-
vent severe disease. Based on these early studies,
multiple society guidelines recommended aggressive
fluid resuscitation in acute pancreatitis [17,18].

Pathophysiologically, these events can be

reflected in patient’s hemodynamic parameters as
tachycardia, hypotension, low central venous pres-
sure, and oliguria; and in routine laboratory values
as hemoconcentration, increased blood urea nitro-
gen (BUN), and creatinine. To prevent the
OBSERVATIONAL DATA IN EARLY
AGGRESSIVE FLUID RESUSCITATION
Subsequently, observational studies evaluated the
efficacy and safety of early aggressive fluid resusci-
tation with conflicting results (Table 1). Two US

Table 1. Summary of observational studies evaluating the effects of aggressive fluid resuscitation in acute pancreatitis

Author, country, Aggressive Nonaggressive Effect of early aggres-

year Design N resuscitation resuscitation sive resuscitation

Eckerwall, Sweden, Retrospective, 99 4 l in first 24 h <4 l in first 24 h Harmful, more respiratory

2006 [21] single center OF, and ICU
Gardner, USA, Retrospective, 45 33% volume <33% volume Beneficial, less mortality
2009 [19] single center administered administered in first
in first 24 h/first 72 h 24 h/first 72 h
Warndorf, USA, Retrospective, 434 33% volume <33% volume Beneficial, less OF, SIRS,
2011 [20] single center administered in administered in first ICU, and LOS
first 24 h/first 72 h 24 h/first 72 h
de-Madaria, Spain, Prospective 247 >4.1 l in first 24 h Moderate: 3.1–4.1 l in first Harmful, more OF
2011 [22] cohort, single 24 h (respiratory and renal),
center Mild: <3.1 l in first 24 h and fluid collections
Singh, USA-Spain, Retrospective, 1010 >1 l in first 4 h <0.5 l in first 4 h Beneficial in first 4 h, less
2017 [25] multicenter or or interventions
>4.3 l in first 24 h <3.2 l in first 24 h Harmful in first 24 h, more
fluid collections
Ye, China, 2019 Retrospective, 112 4.1 l in first 24 h <4.1 l in first 24 h Harmful, more renal OF
[24 ] single center
&

Li, China, 2020 Retrospective, 912 3 ml/kg/h in first 6 h <3 ml/kg/h in first 6 h of Harmful, more NPPV in
[23 ] single center of general wards general wards severe AP, and
&

hemoconcentration

AP, acute pancreatitis; LOS, length of stay; NPPV, noninvasive positive-pressure ventilation; OF, organ failure; SIRS, systemic inflammatory response syndrome.

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single-center retrospective studies, published over a
decade ago, showed a beneficial effect of early resus-
citation with ‘a faster rate’ in clinical acute pancrea-
titis outcomes [19,20]. They reported that early
resuscitation was associated with lower mortality
[19], as well as with fewer ICU admissions, shorter
hospitalization, and lower prevalence of organ fail-
ure [20]. In a subgroup analysis by severity at admis-
sion, a positive effect was only observed in patients
with mild disease, suggesting that severe disease
may not be reversible with early fluid resuscitation
[20]. Even though these studies did not focus on a
specific fluid rate or amount, larger volumes were
administered during the first 24 h in the early group
(3.5–5 l), compared with the late group (<2.5 l),
which supported the notion of early aggressive fluid
resuscitation. In contrast, other observational stud-
ies have raised concerns on the safety of early aggres-
sive fluid resuscitation in acute pancreatitis. These
reports have shown that aggressive fluid resuscita-
tion of more than 4 l within the first 24 h of acute
pancreatitis management, is associated with worse
outcomes, including development of acute respira-
&
tory failure [21,22,23 ], acute kidney injury [22,24 ],
&
and local pancreatic complications [22,25].
The above studies share similar limitations that
need to be considered in the interpretation of their
conclusions. First, causality cannot be established in
an observational study, and it is possible that more
aggressive fluid resuscitation was a response to clin-
ical deterioration. Early mechanisms of severity,
such as vascular leakage and fluid sequestration
manifest clinically as hypovolemia, and critical care
protocols mandate increasing fluid infusion in these
patients, which may further contribute to their
clinical deterioration (reverse causation bias) [26].
Such bias remains on observational studies despite
the use of multivariable analysis controlling for
potential confounders, and the only method to
equalize this bias on treatment arms is through
randomization. Second, most of these studies used
& &
a retrospective design [21,23 ,24 ,25], and it is well
known that clinical data derived from medical
records may not reflect the precise details of fluid
therapy and outcomes, raising concerns for misclas-
sification bias. Third, these studies were conducted
at large referral centers, accepting and treating high
volumes of sick acute pancreatitis patients, which
limits the generalizability of their results to larger
acute pancreatitis populations. Finally, the inter-
ventions included in the aggressive resuscitation
group were heterogeneous within sites and across
studies, reflecting different physician preferences on
fluid onset, rates, type, and cointerventions.
One important lesson from the above observa-
tional studies has been with regards to the
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Intravenous fluid resuscitation Machicado and Papachristou
therapeutic window for ‘early fluid resuscitation’.
When using a 24 h window, individuals under-resus-
citated in the first few hours who receive larger
compensatory fluid amounts afterwards cannot be
differentiated from those aggressively resuscitated
earlier. To prevent this, the research community has
recently shifted the definition of ‘early resuscita-
tion’ towards a shorter therapeutic window of 4–
6 h from initial hospital presentation. This idea was
tested in an international four-center retrospective
study of over 1000 subjects with acute pancreatitis,
which showed that aggressive fluid resuscitation
within the first 4 h (>1 l) was independently associ-
ated with less need for interventions, whereas
aggressive resuscitation over 24 h (>4.3 l) was asso-
ciated with higher risk of local complications [25].
Thus, two phases of fluid resuscitation can be delin-
eated from the time of initial hospital presentation
(Fig. 1).
RANDOMIZED CONTROLLED TRIALS
COMPARING FLUID RESUSCITATION
STRATEGIES
The impact of different fluid resuscitation strate-
gies on acute pancreatitis outcomes has been stud-
ied in four randomized controlled trial (RCTs)
(Table 2). All these studies had small sample sizes,
included heterogeneous populations, adminis-
tered various fluid protocols at different time
points, and were only powered to surrogate out-
comes. We will summarize the design and findings
of these studies, but more importantly, appraise
their limitations to understand their internal valid-
ity, generalizability, and potential lessons for
future study design.
In the first RCT of Mao et al. [27], 76 patients
with severe acute pancreatitis based on the former
Atlanta Classification and signs of volume deficit
were enrolled within 72 h of admission at a single-
center ICU in China and randomized to a rapid (10–
15 ml/kg/h) or controlled (5–10 ml/kg/h) volume
expansion approach. Compared with those in the
control arm, patients receiving rapid expansion had
significantly higher rates of mechanical ventilation
(94 vs. 65%), abdominal compartment syndrome
(72 vs. 32%), sepsis (64 vs. 38%), and mortality
(31 vs. 10%). Methodological concerns with the
design of this RCT include limited description of
the randomization sequence, allocation conceal-
ment, blinding, time of intervention, sample size
calculation, and type of analysis (intention to treat
vs. per protocol); which makes the study highly
biased and limit its interval validity. Furthermore,
the study did not describe the interventions in detail
(onset, duration), and used different types of fluid
www.co-gastroenterology.com 411
Pancreas

FIGURE 1. Comparison of early and late phases of fluid resuscitation. AKI, acute kidney injury; OF, organ failure; SIRS,
systemic inflammatory response syndrome.

solutions in both treatment arms (colloids and crys-
talloids).
Mao et al. [28] conducted a second single-center
RCT, comparing goal-directed fluid therapy targeted
to rapid hemodilution (hematocrit <35%) vs. slow
hemodilution (35%) at 48 h, among 115 subjects
with severe acute pancreatitis based on the former
Atlanta Classification. Participants were randomized
within 24 h of admission, and were infused a mix of
crystalloids and colloids with total volume deter-
mined based on body weight, admission hematocrit,
and goal hematocrit. Compared with controls, the
rapid hemodilution arm was associated with
increased rates of sepsis (79 vs. 58%) and mortality
(44 vs. 15%). The major issue of this study was the use
of quasi-randomization based on patient’s age, in

Table 2. Summary of randomized controlled trials comparing different intravenous fluid resuscitation strategies in acute
pancreatitis
Author, country, Randomi- Aggressive Nonaggressive Effect of early aggressive
year Design N Participants zationa resuscitation resuscitation resuscitation

Mao, China, Superiority 76 Severe AP 72 h Rapid volume Controlled volume Harmful, more sepsis,
2009 [27] expansion expansion (5– mortality, mechanical
(10–15 ml/kg/h) 10 ml/kg/h) ventilation, and ACS
Mao, China, Superiority 115 Severe AP 24 h Rapid hemodilution Slow hemodilution Harmful, more sepsis, and
2010 [28] with goal Hct with goal Hct mortality
<35% at 48 h 35% at 48 h
Wu, USA, Factorial 40 Any severity 6h Goal-directed with LR or NS fluid Similar, SIRS,
2011 [29] 20 ml/kg bolus therapy adjusted and CRP at 24 h
þ 3 or 1.5 ml/ by treating
kg/h of LR or NS physician
Buxbaum, USA, Superiority 60 Predicted 4h 20 ml/kg bolus þ 10 ml/kg Beneficial, less composite
2017 [30] mild AP 3 ml/kg/h of LR bolus þ 1.5 ml/ outcome, SIRS, and
kg/h of LR hemocroncentration

ACS, abdominal compartment syndrome; AP, acute pancreatitis; CRP, C-reactive protein; Hct, hematocrit; LR, lactated Ringer’s solution; NS, normal saline; SIRS,
systemic inflammatory response syndrome.
a
Maximal time interval allowed from time of initial hospital presentation to randomization.

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which the treatment assignment was predictable
before randomization and may have influenced in
the choice of intervention (selection bias). Other
limitations included lack of description on blinding,
sample size calculation, primary outcome, and type
of analysis; which raises concerns for bias and inter-
nal validity of the study.
In a factorial RCT of 40 acute pancreatitis
patients of any severity enrolled within 6 h of initial
hospital presentation at three US centers, Wu et al.
[29] compared four different fluid resuscitation
strategies – physician-directed approach with lac-
tated Ringer’s solution or normal saline vs. goal-
directed approach with lactated Ringer’s solution
or normal saline starting with a 20 ml/kg bolus þ 3
and 1.5 ml/kg/h. The primary outcome was change
of systemic inflammatory response syndrome (SIRS)
at 24 h, and the secondary outcome was C-reactive
protein (CRP) at 24 h. The study had initially
planned to enroll 90 participants, but was termi-
nated earlier, after interim analysis of 40 subjects
showed that 1280 subjects would be needed for
sufficient power. There was no difference of SIRS
reduction at 24 h, CRP level at 24 h, and clinical
outcomes between those who received physician-
directed and goal-directed fluid resuscitation. Sig-
nificantly, there was no difference in the total fluid
volume received by patients in both treatment arms
(4.5 l), which reflects the standardized use of early
aggressive fluid resuscitation by treating physicians.
Major limitations lay in its early termination, small
size, insufficient power for relevant clinical out-
comes, and open-label approach.
In a recent single US center RCT conducted by
Buxbaum et al. [30] 60 acute pancreatitis patients
with predicted mild severity were randomized
within 4 h of initial hospital presentation to either
aggressive (20 ml/kg bolus þ 3 ml/kg/h) or conserva-
tive (10 ml/kg bolus þ 1.5 ml/kg/h) fluid resuscita-
tion with lactated Ringer’s solution. The authors
measured a composite outcome that included
improvement in laboratory parameters from base-
line (hematocrit, BUN, and creatinine), decreased
pain level, and oral tolerance within 36 h. Subjects
assigned to the aggressive fluid resuscitation
approach achieved the primary outcome more fre-
quently than controls (70 vs. 42%), and had lower
risk of SIRS (15 vs. 27%) and hemoconcentration (11
vs. 36%). No patients developed volume overload,
despite receiving a median of 5.6 l in the aggressive
resuscitation arm and 3.9 l in the conservative arm
during the first 24 h. This trial had several strengths
with regards to randomization methods, blinding of
patients, clear definition of interventions, study
power, and use of intention to treat analysis. Lim-
itations include that the study excluded patients
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Intravenous fluid resuscitation Machicado and Papachristou
with SIRS, used a not validated outcome, was
unpowered to detect differences in relevant clinical
outcomes, and did not mask physicians.
Based on the above studies, aggressive fluid
resuscitation can be defined as 20 ml/kg bolus fol-
lowed by 3 ml/kg/h infusion rate. That means
approximately 1500 ml bolus followed by 200 ml/
kg/h infusion rate in an average adult weighting
70 kg. Overall, the results of these RCTs have not
been conclusive about the role of early aggressive
fluid resuscitation in acute pancreatitis; however,
this strategy appears to be effective in patients with
predicted mild disease and may be harmful in those
with predicted severe acute pancreatitis.
SELECTION OF FLUID TYPE
Early animal studies suggested that colloids might be
superior to crystalloids due to less risk for extravascu-
lar leakage and better intravascular flow [13,15].
However, two RCTs that compared 6% hydroxyethyl
starch with crystalloids in severe acute pancreatitis,
showed no difference in mortality across treatment
arms, and higher risk of multiple organ failure with
colloids in one study [31,32]. Hydroxyethyl starch
also lacked any benefit and was associated with seri-
ous adverse events in large, adequately powered,
RCTs of critically ill patients with sepsis [33–35].
Therefore, crystalloids are the standard of care for
fluid resuscitation of acute pancreatitis.
In-vitro and animal studies have shown that
lactated Ringer’s solution has antiinflammatory
properties, reduces trypsin activity, provides extra-
cellular calcium, and lowers pancreatic acidosis;
which offer theoretical advantages of lactated Ring-
&& &
er’s solution over other crystalloids [36 ,37 ,38].
Three RCTs have compared lactated Ringer’s solu-
tion with normal saline, and have shown that lac-
tated Ringer’s solution has a greater impact on SIRS
&& &&
and CRP reduction [29,36 ,39 ]. Although these
studies were not powered for relevant clinical out-
comes, two recent meta-analyses have proposed
both fluid types have a similar effect in mortality
& &&
and organ failure [37 ,40 ]. Given its antiinflamma-
tory properties, lactated Ringer’s solution is sug-
gested as the preferred fluid type for initial fluid
resuscitation in acute pancreatitis, but multicenter
RCTs adequately powered to study relevant clinical
outcomes are needed.
GUIDELINE RECOMMENDATIONS
In the absence of conclusive high-quality data, soci-
ety guidelines have made different recommendations
on fluid resuscitation strategies for acute pancreatitis.
The American College of Gastroenterology (ACG)
www.co-gastroenterology.com 413
Pancreas
Table 3. Practical approach for fluid resuscitation in acute pancreatitis
Time of onset
Fluid type
Initial bolus
Continuous infusion
Setting of fluid initiation
Setting of goal-directed therapy
Frequency of monitoring
Duration of monitoring
Clinical goals
Laboratory goals
Contraindications for
aggressive fluid therapy
Cointerventions
AP, acute pancreatitis; BUN, blood urea nitrogen.
strongly recommended the use of aggressive fluid
resuscitation with 250–500 ml/h of crystalloids in
the first 12–24 h [41]. However, such an aggressive
approach of 6–12 l in 24 h is not evidence-based and
could be harmful in a subgroup of patients. In con-
trast, the International Association of Pancreatology/
American Pancreatic Association (IPA/APA) and the
American Gastroenterological Association (AGA)
have made conditional recommendations about
using ‘goal-directed’ fluid resuscitation based on
low quality of the evidence and weak agreement
&
[42,43 ]. With regard to fluid type, both the ACG
and IPA/APA recommend using lactated Ringer’s
solution, whereas the AGA does not support a specific
&
crystalloid type [41,42,43 ].
QUALITY INDICATORS
Quality indicators have been recently developed by
two different panels of US experts to monitor the
performance of hospitals and clinicians providing
& &
care to acute pancreatitis patients [44 ,45 ]. Both
panels agree that fluid resuscitation with lactated
Ringer’s solution is preferred and should be titrated
according to interval assessments every 8–12 h of
vital signs, urine output, BUN, and hematocrit.
One panel emphasized on the onset of fluid resusci-
&
tation within 2 h of diagnosis [44 ], and the other on
aggressive hydration with at least 3 ml/kg/h unless
&
contraindicated [45 ]. These proposed thresholds
represent desired standards of care; however, they
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Within 4 h of initial hospital presentation, and 2 h of diagnosis
Lactated Ringer’s solution
20 ml/kg
3 ml/kg/h for 12 h; then 1.5 ml/kg/h if parameters improve
Emergency department
General wards or ICUs
12 h
48 h
Hydration parameters
Mean arterial pressure: 65–85 mmHg
Urine output: > 0.5 ml/kg/h
Volume overload parameters
Oxygen saturation: Oxygen saturation >92%
Lung exam: absence of pulmonary crackles
BUN: <20–25 mg/dl
Hematocrit: <44%
Glomerular filtration: >60 ml/min/1.73 m2
Congestive heart failure, end stage renal disease, cirrhosis with volume overload
Early oral nutrition within the first 24 h in predicted mild AP,
proper analgesia, management of organ failure
require further validation in clinical data before
implementation.
WORLDWIDE UTILIZATION
There is great variability on fluid administration
patterns in clinical practice, which is explained by
temporal trends, geographic variations, and per-
&&
sonal preferences [46,47 ]. In a recent, large, pro-
spective, multinational cohort of 1612 acute
pancreatitis patients (APPRENTICE), physicians in
India, Latin America, and North America adminis-
tered more fluids over the initial 24 h (3–3.2 l),
&&
compared with those in Europe (2.5 l) [47 ]. There
was also great variability in the amount of fluids
administered across centers within the same conti-
nent, and within the same center. Most patients in
Europe (77%) and India (92%) were treated with
lactated Ringer’s solution, whereas normal saline
was still more frequently used in the United States
&&
(51%) and Latin America (61%) [47 ].
Based on careful review of the above data and
due to lack of consensus and uniformity adminis-
tering fluids, we herein propose a practical approach
for early fluid therapy in acute pancreatitis (Table 3).
CONCLUSION
Intravenous fluid resuscitation remains the back-
bone of acute pancreatitis management. Aggressive
fluid resuscitation appears to be beneficial when
Volume 36  Number 5  September 2020

started within the first 4 h from hospital presenta-
tion in patients with predicted mild acute pancrea-
titis and administered for duration of 12–24 h. Late
onset of aggressive resuscitation beyond the thera-
peutic window of 4–6 h or in predicted severe acute
pancreatitis might be futile and deleterious. Lac-
tated Ringer’s solution is the preferred fluid type,
given its antiinflammatory effect in preclinical stud-
ies and RCTs. A large, well designed, multicenter
RCT is still required to clarify the role of early
aggressive fluid resuscitation and preferred fluid
type in acute pancreatitis, and to determine the
precise volume, rate, and duration of fluid therapy
required. Such a trial will require close collaboration
between pancreatologists and emergency physi-
cians, using an intense protocol that ensures early
enrollment of subjects with a broad range of pre-
dicted severity, intervention initiation within 4–6 h
of hospital presentation, and sufficient power to
detect differences of relevant and validated
clinical outcomes.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
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Volume 36  Number 5  September 2020