Journal Club Meeting

Dr Isha Bansal
Moderator: Dr Amol Dahale
Journal details
• Published in The New England Journal of Medicine
• Original article
• Title: Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis
• Authors: E. de-Madaria et al.
• Servicio de Aparato Digestivo, Hospital General Universitario Dr.
Balmis, Calle Pintor Baeza 12, Alicante 03010, Spain.
• Published in 15th September,2022
Methodology
• Multi-center , open-label, parallel-group,
• Randomized , controlled, superiority trial,
• Patients were enrolled at 18 centers across four countries (India, Italy,
Mexico, and Spain)
• May 2020 to September 2021,
Inclusion criteria
• Consecutive patients (≥18 years of age) who had received a diagnosis
of acute pancreatitis according to the Revised Atlanta Classification
• (which requires meeting two of the following three criteria: typical
abdominal pain, serum amylase or lipase level higher than 3 times the
upper limit of the normal range, or signs of acute pancreatitis on
imaging)
• The trial included patients who presented to the emergency
department no more than 24 hours after pain onset and who had
received a diagnosis no more than 8 hours before enrollment.
Exclusion criteria
• Patients who met the criteria for Moderately severe or severe disease
at baseline (shock, respiratory failure, and renal failure) or
• baseline heart failure (New York Heart Association functional class II,
III, or IV),
• uncontrolled arterial hypertension, hypernatremia, hyperkalemia,
hypercalcemia,
• an estimated life expectancy of less than 1 year,
• chronic pancreatitis, chronic renal failure, or decompensated cirrhosis
were excluded
• Patients were randomly assigned in a 1:1 ratio to
• receive aggressive fluid resuscitation (aggressive-resuscitation group)
or moderate fluid resuscitation (moderate-resuscitation group) with
the use Of a computer-based central randomization system integrated
in a Web-based electronic form.
• Oral feeding was started at 12 hours if the
• intensity of abdominal pain, as measured on the
• Patient-Reported Outcome Scale in Acute Pancreatitis (PAN-PROMISE),21 was less than 5
(range,
• 0 to 10 for each symptom; overall range, 0 to 70,
• with higher scores indicating higher symptom
• intensity). Fluid resuscitation could be stopped
• once the patient had been able to tolerate oral
• feeding for 8 hours; in the moderate-resuscitation group, this could occur as early as 20
hours
• after randomization, and in the aggressiveresuscitation group as early as 48 hours after
• randomization.
Primary outcome
• Development of moderately severe or severe acute pancreatitis
(according to the Revised Atlanta Classification) during the
hospitalization.
• Moderately severe or severe acute pancreatitis was defined as the
meeting of at least one of the following criteria on the Revised Atlanta
Classification: local complications, exacerbation of a preexisting
coexisting condition, a creatinine level of at least 1.9 mg per deciliter
(170 μmol per liter), a systolic blood pressure of less than 90 mm Hg
despite fluid resuscitation, and a ratio of the partial pressure of arterial
oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of no more than
300.
Secondary outcome
• organ failure and local complications occurring after randomization and during the
hospitalization (see the Supplementary Appendix).16,17 Additional prespecified secondary
outcomes included the duration of hospital stay; intensive care unit (ICU) admission; the
number of days in the ICU; the use of nutritional support or invasive treatment after
randomization and during the hospitalization; the presence of SIRS (see below) at each
checkpoint14; persistent SIRS (lasting >48 hours within the first 72 hours after randomization);
• C-reactive protein levels in blood at 48 hours and 72 hours; death; a composite outcome of
death, persistent organ failure (lasting >48 hours), or infected necrotizing pancreatitis10; and
symptoms as measured with the use of the PANPROMISE scale at admission and each
checkpoint.21 SIRS was defined as the meeting of at least two of the following criteria: a
white-cell count of less than 4000 per cubic millimeter or more than 12,000 per cubic
millimeter, a heart rate of more than 90 beats per minute, a respiratory rate of more than 20
breaths per minute or partial pressure of carbon dioxide of less than 32 mm Hg, or a body
temperature of less than 36°C or more than 38°C.14
Grading of fluid overload
• Fluid overload was graded as mild if it was responsive to medical therapy or
decreased hydration and if the ratio of Pao2
• to Fio2
• never decreased to less than 300; moderate if it was
• responsive to medical therapy or decreased hydration but the ratio of Pao2
• to Fio2
• was lower
• than 300 at least once; and severe if mechanical
• ventilation or hemofiltration was indicated.
Results
• Overall, 249 patients were
• randomly assigned to the aggressive-resuscitation group (122 patients) or the moderate-
resuscitation group (127) and were included in the
• first interim analysis (Fig. S1 in the Supplementary Appendix). The characteristics of the patients
• at baseline were evenly distributed between the
• two trial groups (Table 1). The representativeness of the trial participants with regard to
patients with acute pancreatitis is described in
• Table S1. Sex and cause of disease were representative of patients with acute pancreatitis, but
• age was younger, which was expected, owing to
• the exclusion of certain coexisting conditions
• that are associated with older age (e.g., heart or
• kidney failure).1
• Volume overload was managed as
• follows: by decreased hydration alone in 12.0%
• of the patients in the aggressive-resuscitation
• group and in none of those in the moderateresuscitation group; by
diuretics in 88.0% and
• 100%, respectively; and by inotropes in 8.0% and
• none, respectively
• One patient in the aggressiveresuscitation group underwent
orotracheal intubation, and no patient underwent hemofiltration.
• The median time from randomization to
• fluid overload was 34 hours (interquartile range,
• 22 to 46) in the aggressive-resuscitation group
• and 46 hours (interquartile range, 30 to 64) in the moderate-
resuscitation group
• Fluid
• resuscitation was associated with symptoms of
• fluid overload in 18.0% of the patients in the
• aggressive-resuscitation group and in 7.9% of
• those in the moderate-resuscitation gro
Discussion
• This trial showed that aggressive fluid resuscitation increased the risk
of volume overload.
• An increased risk of fluid overload was detected in the overall
population of
• patients and also in subgroups of patients without SIRS at baseline,
patients with SIRS at baseline (thus, with a higher risk of deve
Limitation
• Nevertheless, there are several limitations to
• consider. This trial was terminated at the first
• interim analysis; thus, it is underpowered to
• evaluate efficacy outcomes definitively. However,
• given the small between-group difference in the
• risk of moderately severe or severe acute pancreatitis, the data and safety monitoring board was
• concerned that a much larger sample size would
• be needed for the trial to show superiority in
• either group, which would expose many patients
• to a much higher risk of fluid overload.1,34 The
• same ethical issues and decision making affected the Fluid Expansion as Supportive Therapy
• (FEAST) trial, in which intravenous boluses of
• fluid were associated with unfavorable outcomes
• in children with severe infection.35,36
• Another limitation is that this randomized,
• controlled trial was open-label, which may have
• introduced bias. Nevertheless, the requirement
• for trial physicians to evaluate patients sequentially and to adjust the fluid rate to address
• volume overload or hypovolemia made doubleblinding impractical
Conclusion
• In our randomized assessment of aggressive
• fluid resuscitation as compared with moderate
• fluid resuscitation for the treatment of acute
• pancreatitis, the use of aggressive fluid resuscitation led to a higher
risk of volume overload
• and did not show the hypothesized benefit in
• disease-specific outcomes.