4. Discussion
Due to pancreatic and extra-pancreatic necrosis, acute pancreatitis (AP)
is largely secondary to infection and causes Multiple organ dysfunction
syndrome (MODS), which is a inflammatory disease with high morbidity and
mortality64. Researchs have shown that during the
pathogenesis of AP, neutrophils, lymphocytes, monocytes, natural killer
cells and endothelial cells can produce a variety of cytokines or
inflammatory mediators such as TNF-α, IL-1 and IL-6, and then induce
inflammatory response or reduce cellular immune response through various
pathways65. Early treatment in intensive care units
has been recognized to be of great benefit to patients with severe
episodes. Patients with AP are generally divided into three subgroups:
mild, moderate, and severe. It is necessary to adjust the treatment
regimen according to their specific needs, but determining the severity
of the disease remains a clinical challenge. Serum markers are generally
regarded as important indicators to predict the severity of AP. Serum
C-reactive protein (CRP) is an acute phase reactant synthesized by the
liver. In response to inflammation and infection, its levels in the
blood increase within hours. Especially in inflammatory diseases, it is
often used in infection and inflammation follow-up due to its short
half-life, easy measurement and close relationship with prognosis of the
disease66. In many textbooks, CRP is still considered
as a gold standard for disease severity assessment67.
Studies have reported that low serum
albumin is independently associated with an increased risk of persistent
organ failure and death in acute pancreatitis and can be used to predict
the severity of acute pancreatitis68.
Continuous renal replacement therapy (CRRT) is defined as a blood
purification treatment technique that continuously and slowly removes
water and solutes by means of extracorporeal circulation blood
purification to replace renal function. Compared with common
hemodialysis, CRRT can prolong the treatment time of blood purification
and reduce the treatment efficiency per unit time, so as to minimize the
impact of changes in the concentration and volume of solute in blood on
the body. Meanwhile, it adopts a filter with high permeability and good
biocompatibility. It provides an important homeostasis balance for the
treatment of severe patients. With the continuous development of science
and technology, CRRT has new functions in addition to regulating water
and electrolyte, maintaining acid-base balance and removing metabolic
wastes69. Its application scope is no longer limited
to kidney disease, and began to be used in the treatment of non-renal
failure diseases such as pancreatitis13.Early CRRT can
reduce the fatality rate of AP patients, as early as 2006 JPN Guideline
wrote CRRT into the treatment of AP70. Researches have
shown that CRRT can effectively remove the components of damaged
vascular endothelial cells, improve endothelial cell function, thus
reducing the incidence of MODS, and can delay or even block the process
of MODS71.
This meta-analysis, which was based on 53 RCTs including 3382
participants, found that CRRT may indeed more beneficial to AP patients
than conventional treatment. The study showed that after CRRT treatment,
the mortality rate of the CRRT group was significantly lower than that
of the control group, and there was no obvious heterogeneity between the
groups, and the difference was statistically significant. CRRT also
significantly reduced the APACHEⅡscores and cleared serum amylase and
markers of the patients, and was superior in inflammatory factor
clearance rate, alleviate the liver and kidney injury and without
significant adverse reactions. According to the data of each research
scope is different, we carried out subgroup analysis for serum
inflammatory markers, liver and kidney function, APACHE Ⅱ scores. We
found that there was less heterogeneity within the subgroup (less than
50%) after grouping according to data range, but greater heterogeneity
(90%) between groups as a whole. However, there were statistically
significant differences in the results, shown the efficacy of CRRT
treatment was better. Therefore, we believe that the inter-group
heterogeneity is mainly due to clinical heterogeneity, that is, the
severity of AP patients in different studies is different, so that the
datas of outcome indicators is different.
The difference between the meta-analysis in our study and the previous
meta-analysis are the following : First of all, our study covered a
large number of RCT studies and was not limited by language. A total of
3,392 subjects were included, with a larger sample size. Secondly,
despite the past research done on meta-analysis of CRRT treatment of
acute pancreatitis, but does not involve that much serum markers of
inflammation factors and discuss the effects on liver and kidney
function. As an updated and more comprehensive meta-analysis, this study
further strengthened previous meta-analysis results, focused on more
representative and specific results, fully described the impact of CRRT
on AP patients, and strengthened the persuadability of existing
evidence. Third, we registered the agreement of this study with PROSPERO
in order to enhance PROSPERO’s transparency and quality of this
meta-analysis.
From the perspective of the included literature content, the original
research has several limitations due to the defects in design,
measurement and evaluation. First of all, the randomized controlled
trials included in this meta-analysis were conducted in different
patient groups and in different clinical Settings. Therefore, potential
heterogeneity risk exists. Secondly, although baseline status was
compared between groups in each study, due to the different degree of AP
patients included in the meta-analysis, the baseline status varied
widely from study to study, various outcome indicators in different
studies may also be different, which is also considered as the main
source of heterogeneity in some outcome indicators. Thirdly, since CRRT
treatment is significantly different from conventional treatment,
doctors and patients cannot be blinded, which may cause performance bias
and observation bias. Fourthly, due to the different conditions of
different patients and the different time of CRRT treatment, the
experimental results may be affected. Finally, the causes of these AP
patients are different, and the description of whether they have
diabetes, hypertension and other underlying diseases is not detailed.