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 Table of Contents  
Year : 2022  |  Volume : 4  |  Issue : 1  |  Page : 6

Update of Thoracic Epidural Analgesia Used in Acute Pancreatitis

Department of Critical Medicine, Affiliated Hospital of Zunyi Medical University; Guizhou Severe Acute Pancreatitis Diagnosis and Treatment Center, Zunyi, Guizhou Province, China

Date of Submission24-Oct-2021
Date of Acceptance16-Feb-2022
Date of Web Publication17-Mar-2022

Correspondence Address:
Dr. Xiaoyun Fu
Department of Critical Medicine, Affiliated Hospital of Zunyi Medical University, Dalian Road 149, Zunyi 563003, Guizhou Province
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JTCCM-D-21-00021

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Acute pancreatitis (AP) is one of the common gastrointestinal diseases requiring hospitalization. Once AP develops into severe AP, the mortality markedly increases. Animal studies have confirmed that thoracic epidural analgesia (TEA) has many benefits for AP and can provide the survival rate of experimental animals. Existing clinical studies have also shown the safety and effectiveness of TEA in AP. This paper reviews the potential benefits and possible mechanisms of TEA for AP.

Keywords: Acute pancreatitis, mortality, perfusion, thoracic epidural analgesia

How to cite this article:
Fu B, Geng Z, Fu X. Update of Thoracic Epidural Analgesia Used in Acute Pancreatitis. J Transl Crit Care Med 2022;4:6

How to cite this URL:
Fu B, Geng Z, Fu X. Update of Thoracic Epidural Analgesia Used in Acute Pancreatitis. J Transl Crit Care Med [serial online] 2022 [cited 2023 Mar 31];4:6. Available from: http://www.tccmjournal.com/text.asp?2022/4/1/6/339790

  Introduction Top

Acute pancreatitis (AP) is one of the common gastrointestinal diseases requiring hospitalization, with an annual incidence of 34/100,000 person in high income countries.[1] In about 80% of patients, AP manifests as mild edematous pancreatitis, and these patients will be discharged after a few days of treatment.[2] However, there are still approximately 20% of cases that rapidly deteriorate into severe AP (SAP), which is characterized by the presence of a transient (<48 h) or persistent organ failure (>48 h) or complications. Once SAP develops, the severity of the disease, length of hospital stay, treatment cost, and mortality rate will increase significantly, and the mortality rate can reach 30%.[3] In recent years, the global incidence of AP has been increasing year by year.[4] The increase in the incidence of AP may be related to the improvement of the dietary conditions of the global population, the increase in obesity, the increase in the incidence of gallstones, and the increase in alcohol consumption. There are differences in the etiology of pancreatitis in different regions around the world. Biliary and alcoholic pancreatitis are mainly found in Europe and North America, and biliary and hyperlipidemic pancreatitis are mainly found in China.[5]

A prominent symptom of AP is abdominal pain. Thoracic epidural analgesia (TEA) is a key tool for anesthesiologists for acute pain management. TEA is especially effective for reducing pain after chest and upper abdominal surgery. Initially, TEA was primarily used to manage abdominal pain in AP patients. However, subsequent animal and clinical studies demonstrated additional benefits of TEA for AP. Therefore, the therapeutic effect of TEA on AP has attracted extensive attention in recent years. Therefore, this paper reviews the advantages of TEA in the treatment of AP.

  Thoracic Epidural Analgesia Technology Top

The beneficial effects of TEA require that catheter placement and the infusate be targeted at the thoracic segments that innervate the injured skin, muscle, and bone from which nociceptive inputs originate.[6] The most percutaneous access to the thoracic epidural space involves puncture guided by superficial anatomical landmarks. The prominent C7 spinous process, the scapular spine (T3), and the inferior border of the scapula (T7) are useful landmarks for approximating the puncture site to the intended segment. It may be useful to estimate the target thoracic segment in obese patients using the prominent C7 spinous process. Counting from the iliac crest improves the accuracy of epidural placement in the lower thoracic segment (T10 to T12). After contrast injection, fluoroscopy can be used to guide placement of precise segments and to verify proper catheter placement. The use of ultrasound to facilitate placement of epidural catheters has been performed clinically.[7]

Because of the extreme caudad angulation of the thoracic spinous processes, a conventional midline approach to the thoracic epidural space can be difficult. A paramedian approach is required to keep the needle consistent over most other thoracic epidural segments above T11. The main options for YEA analgesics include local anesthetics alone, opioids alone, or a combination of local anesthetics and opioids. The choice of monotherapy or combination therapy usually depends on the characteristics of the patient. The median duration of TEA in AP patients was 11 days (interquartile range [IQR]: 8–16), with extreme values ranging from 3 to 38 days.[8] Among 4185 patients treated with TEA, the overall incidence of complications was 3.1%. This included unsuccessful catheter placement (1.1%), dural puncture (0.7%), post-operative radicular pain (0.2%), and peripheral nerve injury lesions (0.2%).[9] Another retrospective study involving 2837 patients undergoing TEA cardiac surgery showed no epidural hematoma or abscess and only two superficial skin infections at the insertion site (0.07%).[10] Adverse reactions associated with drugs used in TEA include nausea, vomiting, pruritus, hypotension, urinary retention, sedation, and respiratory depression. Therefore, TEA is safe and feasible for patients with AP.

  Effect of Thoracic Epidural Analgesia on Pancreas Top

The rationale for using TEA in AP is that intestinal and hepatic perfusion are modulated by sympathetic and parasympathetic nerves. In the resting state, sympathetic tone is low and blood flow is primarily regulated by vagal tone activity. During acute stress and pain, sympathetic nerve activity increases, resulting in intestinal vasoconstriction and a decrease in blood flow.[11]

Previous studies have shown that pancreatic blood flow is reduced in the early stage of AP, and this reduction in blood flow may play a role in the conversion of edematous to necrotizing AP.[12],[13],[14],[15] Epidural anesthesia (EA) is widely used to alleviate analgesia in the perioperative period and reduce pain in patients with AP.[16] Demirag et al. first demonstrated that TEA partially restored the decrease of pancreatic microcirculation flow caused by AP and prevented development of tissue necrosis in the rat model of AP.[17] Therefore, the authors proposed that TEA should be considered as a treatment option to prevent evolution from edematous to necrotic AP. In 2013, a randomized experimental trial was performed in 34 pigs with AP.[18] The results showed that TEA significantly enhanced microcirculatory perfusion and tissue oxygenation of the pancreas.[18] Sadowski et al. used a perfusion protocol of computed tomography scan to evaluate pancreatic blood flow in human and also found that TEA increased arterial perfusion of the pancreas.[19]

  Effect of Thoracic Epidural Analgesia on Liver Top

In the pathogenesis of AP, the activation of sympathetic nervous system leads to the increase of catecholamines and induces the activation of hepatocytes, Kupffer cells, and neutrophils.[20] Cytokines interleukin-6 and tumor necrosis factor neutrophils can cause systemic inflammation, leading to local liver injury and hepatocyte apoptosis.[20] The sympathetic nerve activity plays an important role in liver damage and immune reaction. Sympathetic block is considered as a pivotal mechanism of the protective effects of TEA.[21],[22] A previous animal study showed that TEA could prevent sinusoidal vasoconstriction and decreased apoptotic cell death after AP but did not affect leukocyte adhesion.[11] These results suggested that TEA reduces hepatic injury in necrotizing AP, which may be related to the regional sympathetic nerve block. Hence, TEA may preserve hepatic function in systemic inflammatory disease such as AP. However, there is still a lack of randomized controlled trial studies to confirm the protective effect of TEA on AP-related liver damage.

  Effect of Thoracic Epidural Analgesia on Gastrointestinal Tract Top

During hemorrhage-induced intestinal perfusion injury, Adolphs et al. detected an improvement in microcirculation after TEA.[23] A previous study has shown that EA can shorten the time of intestinal paralysis after laparotomy or abdominal surgery, and this effect can be explained by blocking the sympathetic efferent nerve.[24] In addition, TEA increased intestinal mucosal blood flow and decreased intermittent flow in the villus microcirculation in the case of a decreased perfusion pressure.[25] During hemorrhagic hypotension and after resuscitation, TEA alleviates hemorrhage-induced impairment of gut perfusion in rats.[23] Another study also showed that TEA attenuates endotoxin-induced impairment of intestinal perfusion.[26] The above animal studies have shown the benefits of TEA on gastrointestinal tract. TEA has been shown to reduce the duration of postoperative ileus compared with systemic opioid therapy in abdominal surgery patients.[27],[28] Recovery from postoperative ileus was earlier with epidural local anesthetic alone than with combined epidural opioids and local anesthetic.[29] The improvement of intestinal motility by TEA may be related to the following two mechanisms. First, TEA can reduce gastrointestinal hypomotility induced by systemic opioids. Second, thoracic cutaneous segmental blockade of the local anesthetic TEA inhibits nociceptive afferent and sympathetic efferent activity while leaving the vagal parasympathetic innervation intact.

AP is a common acute abdominal disease with gastrointestinal disorder. The gastrointestinal tract is the largest organ of the human body and provides a broad colonization surface for the flora. Most of the bacteria that cause necrotizing infections of pancreatic tissue come from the gut flora, such as  Escherichia More Details coli and Enterococcus.[30] Consequently, intestinal function may take a key role in the development of SAP. Animal studies showed gut microcirculatory injury and intestinal hypoperfusion both in edematous and in necrotizing pancreatitis.[31],[32],[33] Freise et al. have found that TEA improves ileal mucosal capillary perfusion and decreases the mortality rate in rats with SAP.[34] The clinical study of TEA improving gastrointestinal perfusion and microcirculation has not been reported.

  Effect of Thoracic Epidural Analgesia on Lung Top

A meta-analysis of randomized controlled trials comparing TEA with opioids and local anesthetics to systemic opioids showed significantly lower rates of atelectasis, pulmonary infection, hypoxemia, and overall pulmonary complications.[35] Compared with systemic opioids, epidural analgesia provided better pain management, reduced myocardial infarction, time to tracheal extubation, postoperative respiratory failure, gastrointestinal bleeding, and intensive care unit (ICU) stay.[36] TEA appears to improve diaphragmatic dysfunction after thoracoabdominal surgery by reducing the inhibitory effect of surgical injury on phrenic motor neuron activity.[37] Recent studies have shown that the incidence of pneumonia with systemic analgesia has dropped from 34% to 12% over the past few decades, while the incidence of pneumonia with TEA remains about 8%.[38] Therefore, TEA can reduce pulmonary complications. Can tea improve pulmonary complications caused by AP?

Acute lung injury (ALI) often occurs in patients with SAP. Hypoxemia, lung infiltration, and pleural effusion may occur as complications of AP. ALI caused by AP is characterized by endothelial cell injury, intra-alveolar edema, white blood cell isolation, and increased nitric oxide (NO) production.[39] The increase in NO production has an adverse effect on vascular reactivity and leads to the destruction of endothelial permeability and integrity, which leads to a decrease in responsiveness to hypoxia and an increase in shunting. In experimental pancreatitis, TEA decreased pulmonary shunting, increased gas exchange, and reduced exhaled nitrous oxide (exNO) concentration.[40] Furthermore, TEA partially restores receptor-dependent pulmonary vasoconstriction (AngII) and hypoxic pulmonary vasoconstriction.[40] In the dog's one-lung ventilation model, TEA does not affect vascular tone but can enhance blood flow shunting and improve arterial blood oxygenation.[41] The mechanism by which TEA affects lung function may originate from segmental sympathetic nerve block, which redistributes the segmental blood flow to the intestine with the maintenance or enhancement of sympathetic nerve activity. Our recent retrospective study showed that SAP patients who received TEA had a lower incidence of acute respiratory distress syndrome than those who did not receive TEA (46.0% vs. 62.4%, P = 0.0044).[42]

  Effect of Thoracic Epidural Analgesia on other Organs Top

The pathophysiology of acute kidney injury (AKI) in AP is not well understand. The premature activation of pancreatic enzymes within the acinar cells causes automatic digestion of the pancreas and surrounding tissues, which triggers a series of events leading to AKI.[43] Our research team used ultrasound microbubble technology to observe the effects of TEA on renal blood flow in AP. We observed the changes of time to peak (Ttop), base intensity (BI), and peak intensity (PI) before and after TEA. The results showed that Ttop after TEA was significantly shorter than that before TEA (7.6 ± 2.2s vs. 11.7 ± 2.6s, P < 0.05), but there was no significant change in Bi and PI before and after TEA (Unpublished). Our retrospective study showed that SAP patients who received TEA had a lower incidence of AKI than those who did not receive TEA (27.7% vs. 45.3%, P = 0.0044).[42] Our results seem to suggest that TEA may have potential benefits for SAP-induced renal injury, but animal studies are still needed to confirm the benefits.

In addition to the effect on organ function, TEA also has effects on metabolism. A previous experimental study showed that TEA improved metabolic acidosis, decreased the severity of pancreatic necrosis score and serum amylase concentrations in rats with AP.[17] In another experimental AP, TEA reduces insulin resistance and inflammatory response.[44]

  Clinical Study of Thoracic Epidural Analgesia in Acute Pancreatitis Top

EA is one of the most effective methods of pain control during perioperative period.

In many medical centers, TEA is often used for pain control caused by AP and is very effective. Although animal experiments have shown the potential benefits of TEA in the treatment of AP, there is still a lack of strong clinical evidence. At present, most clinical studies of TEA for AP are observational studies. An observational study of 121 patients showed that EA could be safely used in ICU without serious complications.[8] In this study, the median duration of EA was 11.0 days (IQR: 8–16). In 2002, a prospective study of 121 patients founded that 72% of patients receiving TEA no longer need the systemic use of other analgesic substances and only 8% of patients have hemodynamic instability that requires intervention.[16]

A prospectively randomized research of 35 patients demonstrates that TEA enhances pancreatic artery perfusion and improves the clinical prognosis of patients with AP.[19] In this study, the median length of TEA was 5.7 days and no complication of TEA was founded. A randomized controlled study found that the decrease in serum procalcitonin in the TEA group was significantly greater, but the mortality rate did not decrease significantly.[45] At present, the evidence supporting the application of TEA in patients with AP is a multicenter propensity analysis in 2018.[46] This study used propensity analyses to minimize for bias in therapy assignment and prognostic imbalances. The results suggested that the mortality of patients in the TEA group was lower than that of patients who did not receive TEA (4% vs. 22%, P = 0.003) and TEA was an independent predictor of 30-day mortality after adjustment (adjusted odds ratio, 0.10; (95% confidence interval 0.02–0.49); P = 0.004). Our study also showed that the mortality of SAP patients in early TEA was lower than that in those who did not receive TEA (4.8% vs. 15.3%, P = 0.0263). Previous study and our study supports the use of TEA as a therapeutic intervention for AP.

  The Future and Prospect Top

Although animal experiments and clinical studies have confirmed the benefits of tea for AP, we still look forward to a multicenter randomized control trial Epidural analgesia for pancreatitis.[47] This study will provide an important insight on role of TEA in the management of AP.

There are still many problems to be explored in the application of TEA in patients with AP. When does TEA start? Does the earlier the TEA initiate, the more patients will benefit? Are there differences in the benefits of TEA for pancreatitis of different etiologies? Can patients with SAP complicated with sepsis receive TEA treatment? In summary, TEA appears to be a very promising intervention in the management of AP. In the future, more research is needed to explore its mechanism and clinical efficacy.

Financial support and sponsorship

This review was funded by the National Natural Science Foundation of China (No. 82160362).

Conflicts of interest

There are no conflicts of interest.

  References Top

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