Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT06327230 |
| Other study ID # |
SRRSH2023-0627 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2024 |
| Est. completion date |
April 30, 2026 |
Study information
| Verified date |
March 2024 |
| Source |
Sir Run Run Shaw Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Acute pancreatitis (AP) is one of the most common diseases of the digestive system, with its
incidence increasing year by year. 15%-25% of patients will develop severe acute pancreatitis
(SAP), characterized by necrosis and infection of the pancreas and surrounding tissues, as
the investigators as multiple organ dysfunction syndrome (MODS), with a mortality rate as
high as 17%. Currently, there is a lack of effective measures in clinical practice to
regulate the early inflammation and immune response in acute pancreatitis. Animal
experimental studies have confirmed that TEA, by blocking the abdominal sympathetic nerves,
increases arterial blood flow and venous capacity, improves pancreatic perfusion
insufficiency caused by AP, and alleviates metabolic acidosis. Simultaneously, TEA can
suppress the secretion of catecholamines during the stress state of acute pancreatitis,
reducing the release of inflammatory mediators and thereby inhibiting the inflammatory
response. Our team's earlier animal experiments have further confirmed that TEA improves
intestinal inflammation in mice with pancreatitis. This improvement is marked by a
significant reduction in the concentrations of inflammatory cytokines such as IL-1β and
TNF-α. Additionally, there is an observed alteration in the intestinal microbiota,
characterized by an increase in the proportion of beneficial bacteria. Based on these
findings, it is speculated that TEA, by reducing catecholamine release and downregulating
sympathetic activity, effectively mitigates inflammation and stress responses in patients
with pancreatitis. Furthermore, TEA dilates small arteries in blocked segments, thereby
improving blood flow and microcirculation within the affected area. Indirectly, TEA increases
vagal nerve activity, which in turn slows down the progression of intestinal ischemia,
consequently reducing the impact of the "second hit" caused by the translocation of
intestinal bacteria and endotoxins into the bloodstream, which exacerbates acute
pancreatitis. Despite these promising results, clinical data on the efficacy of TEA in acute
pancreatitis remains insufficient. Moreover, the precise mechanisms by which TEA influences
the progression and severity of acute pancreatitis are yet to be fully elucidated. In order
to further validate the clinical therapeutic effects of TEA and gain a deeper understanding
of its mechanisms, the investigators have conducted this clinical study.
Description:
Acute pancreatitis (AP) is one of the most common diseases of the digestive system, with its
incidence increasing year by year. 15%-25% of patients will develop severe acute pancreatitis
(SAP), characterized by necrosis and infection of the pancreas and surrounding tissues, as
the investigators as multiple organ dysfunction syndrome (MODS), with a mortality rate as
high as 17%. This poses a serious threat to public health and also imposes a heavy burden on
medical resources. Further improving the treatment level of acute pancreatitis (especially
severe cases) is an urgent problem that needs to be addressed.
Acute pancreatitis is a systemic disease. In the early stages of onset, along with local
inflammation in the pancreas, there is a release of a large number of inflammatory mediators,
leading to systemic inflammatory response syndrome (SIRS). This can subsequently affect
multiple systems including respiratory, circulatory, urinary, digestive, and nervous systems,
with severe cases leading to multiple organ dysfunction syndrome (MODS). The necrosis and
infection of the pancreas and surrounding tissues can lead to a series of local and systemic
complications. It has been confirmed that necrosis, infection, and organ dysfunction are the
main reasons for the poor prognosis of pancreatitis. During the acute phase of pancreatitis,
systemic inflammatory cells become excessively activated and release large amounts of
cytokines, triggering a cascade reaction of inflammatory mediators, leading to systemic
inflammatory response syndrome (SIRS) and subsequently inducing multiple organ dysfunction
syndrome (MODS). The release of inflammatory factors also leads to damage to the intestinal
mucosal barrier, allowing harmful substances or bacteria to pass through the damaged
intestinal mucosal barrier into the bloodstream or invade other organs outside the
intestines, further exacerbating the development of acute pancreatitis. Following the initial
phase of acute inflammation and subsequent translocation of intestinal bacteria and
endotoxins into the bloodstream, creating a "second hit," the mortality rate of pancreatitis
can reach as high as 10-24%.
Currently, there is a lack of effective measures in clinical practice to regulate the early
inflammation and immune response in acute pancreatitis. In recent years, studies have shown
that the nervous, endocrine, and immune systems can interact with each other, exerting mutual
constraints and playing important roles in the inflammatory stress response6. Thoracic
Epidural Anesthesia (TEA) is a commonly used method of nerve blockade in anesthesia. It
involves injecting local anesthetic drugs into the epidural space to block the nerve roots,
resulting in paralysis of the innervated area. TEA is widely used for postoperative pain
management in thoracic and abdominal surgeries. In patients with acute pancreatitis (AP), TEA
can block the transmission pathway of visceral sensory pancreatic pain fibers to the brain,
thereby reducing the patient's pain and stress response caused by pain, and alleviating the
patient's suffering. Low concentrations of local anesthetics can effectively block the
sympathetic nerves corresponding to the segment, by reducing sympathetic nerve tension,
dilating small arteries in the corresponding segment, and improving blood flow and
microcirculation in the blocked area. Animal experimental studies have confirmed that TEA, by
blocking the abdominal sympathetic nerves, increases arterial blood flow and venous capacity,
improves pancreatic perfusion insufficiency caused by AP, and alleviates metabolic acidosis.
Simultaneously, TEA can suppress the secretion of catecholamines during the stress state of
acute pancreatitis, reducing the release of inflammatory mediators and thereby inhibiting the
inflammatory response. Furthermore, the excessive release of early inflammatory factors in
acute pancreatitis (AP) and ischemia-reperfusion injury, among other factors, lead to the
release of intestinal bacterial endotoxins into the bloodstream. This triggers a burst
release of pro-inflammatory cytokines such as IL-1β and IL-18, which further exacerbates the
damage to the intestinal mucosal barrier. Consequently, this imbalance in the microecological
environment causes intestinal mucosal edema, erosion, and initiates a vicious cycle of
systemic inflammatory response, leading to multi-organ damage and dysfunction. This cycle is
a significant contributor to the high mortality and disability rates associated with severe
acute pancreatitis. TEA selectively blocks the efferent sympathetic nerve fibers in the
thoracic and abdominal segments, indirectly increasing vagal nerve activity. This promotes
gastrointestinal motility, improves intestinal blood circulation, slows down the progression
of acute intestinal ischemia, and prevents the translocation of intestinal bacteria and
endotoxins across the intestinal mucosa. Our team's earlier animal experiments have further
confirmed that TEA improves intestinal inflammation in mice with pancreatitis. This
improvement is marked by a significant reduction in the concentrations of inflammatory
cytokines such as IL-1β and TNF-α. Additionally, there is an observed alteration in the
intestinal microbiota, characterized by an increase in the proportion of beneficial bacteria.
Based on these findings, it is speculated that TEA, by reducing catecholamine release and
downregulating sympathetic activity, effectively mitigates inflammation and stress responses
in patients with pancreatitis. Furthermore, TEA dilates small arteries in blocked segments,
thereby improving blood flow and microcirculation within the affected area. Indirectly, TEA
increases vagal nerve activity, which in turn slows down the progression of intestinal
ischemia, consequently reducing the impact of the "second hit" caused by the translocation of
intestinal bacteria and endotoxins into the bloodstream, which exacerbates acute
pancreatitis. Despite these promising results, clinical data on the efficacy of TEA in acute
pancreatitis remains insufficient. Moreover, the precise mechanisms by which TEA influences
the progression and severity of acute pancreatitis are yet to be fully elucidated.
In clinical practice, epidural blockade often employs low-concentration local anesthetics
combined with opioid medications. Hydromorphone, a semi-synthetic potent opioid, when
administered perispinally, not only enhances analgesic effects but also exhibits superior
vasodilatory properties compared to other opioids such as epidural morphine and fentanyl.
This carries particular clinical significance in improving pancreatic microcirculation in
patients with acute pancreatitis (AP).
In this study, the investigators propose employing ropivacaine in combination with
hydromorphone for TEA. Our aim is to analyze the inflammatory response and clinical efficacy
in patients with acute pancreatitis following the early application of TEA, and to elucidate
its protective mechanisms.
