INTRODUCTION — Pancreatic cancer, cancer metastatic to the pancreas, and chronic pancreatitis are commonly associated with intense pain. Pharmacologic therapy such as nonsteroidal agents and opioids may be inadequate for controlling pain. In addition, opioids have been associated with side effects such as nausea and constipation and with concerns of opioid misuse and dependence. Non-pharmacologic therapies to control pain include nerve blocks that involve injection of a drug in proximity to the celiac plexus to provide analgesia. Interventions targeting the celiac plexus have been performed percutaneously with computed tomography-guidance or intraoperatively, while the endoscopic ultrasound (EUS)-guided approach has been increasingly utilized in clinical practice.
This topic will review EUS-guided celiac plexus and other targeted interventions for managing pain related to pancreatic cancer and chronic pancreatitis.
The diagnosis and management of pancreatic cancer are discussed separately. (See "Clinical manifestations, diagnosis, and staging of exocrine pancreatic cancer" and "Treatment for potentially resectable exocrine pancreatic cancer" and "Treatment protocols for pancreatic cancer".)
Assessment of cancer pain and the use of non-EUS interventions for managing pain are discussed separately:
●(See "Assessment of cancer pain".)
The clinical manifestations, diagnosis, and treatment of chronic pancreatitis are discussed separately. (See "Chronic pancreatitis: Clinical manifestations and diagnosis in adults" and "Chronic pancreatitis: Management".)
ANATOMY OF THE CELIAC PLEXUS — The celiac plexus is a dense network of nerves including sympathetic and parasympathetic efferent fibers and visceral sensory afferent fibers that innervate the upper abdominal organs . The celiac plexus mediates the sensation of pain from the pancreas and includes right and left ganglia that lie anterolateral to the aorta at the origin of the celiac trunk (ie, the first large vessel to branch from the aorta below the diaphragm). The celiac ganglia are typically located between T12 and L2 and, in most patients, two to five large ganglia are present . The celiac ganglia receive the splanchnic nerves from T5 to T12, which connect at the celiac plexus and pass through the crus of the diaphragm onto the spinal cord . The terms celiac plexus and splanchnic nerves are often used interchangeably, although they are anatomically distinct structures . Stimuli reach the thalamus and cortex of the brain, and this information is perceived as pain. Descending inhibitory mechanisms may also modulate the ascending pain information.
TERMINOLOGY — Therapeutic nerve blocks involve injection of a drug in proximity to a nerve to provide pain relief. EUS-guided celiac plexus interventions involve drug injections at the level of the celiac artery.
Common celiac plexus interventions are divided into the following:
●Celiac plexus neurolytic block (ie, celiac plexus neurolysis) – EUS-guided celiac plexus neurolytic block is an intervention that permanently alters the affected nerve.
●Celiac plexus nonneurolytic block (ie, celiac plexus block) – EUS-guided celiac plexus nonneurolytic block is an intervention that interrupts nerve transmission without permanently injuring the affected nerve.
Other EUS-guided celiac plexus interventions include:
●Celiac ganglia neurolytic block – EUS-guided celiac ganglia neurolytic block is an intervention involving drug injection directly into the celiac ganglia (also referred to as celiac ganglia neurolysis or simply celiac neurolysis).
●Broad plexus neurolytic block – EUS-guided broad plexus neurolytic block (or broad plexus neurolysis) involves injecting a neurolytic agent at the level of the superior mesenteric artery, resulting in a broader distribution of neurolytic block. This is sometimes referred to as an extended celiac neurolysis.
CONTRAINDICATIONS — There are few contraindications to EUS-guided celiac plexus interventions; however, most contraindications are related to routine upper endoscopy and include:
●Patients who cannot tolerate moderate sedation, monitored anesthesia care, or general anesthesia. (See "Anesthesia for gastrointestinal endoscopy in adults".)
●Patients who are hemodynamically unstable.
●Patients with abnormal coagulation studies (platelet count <50,000/microL; international normalized ratio >1.5). (See "Gastrointestinal endoscopy in patients with disorders of hemostasis".)
CELIAC PLEXUS INTERVENTIONS
Neurolytic block (celiac plexus neurolysis)
Patient selection — Neurolytic block is indicated for relief of abdominal pain in patients with inoperable pancreatic cancer (or a malignancy with pancreatic metastasis) who require opioid analgesics or who do not wish to use opioids . EUS-guided celiac plexus neurolysis produces analgesia by destroying (ie, causing lysis in) afferent neural pathways or sympathetic structures involved in pain transmission. Neural destruction can be achieved by injecting material (typically alcohol plus local anesthetic) that damages the nerve.
Early referral for EUS-guided-celiac plexus neurolysis has been associated with better pain control and less opioid consumption compared with waiting until after failure to obtain pain relief with opioids [5,6]. When on-site cytopathology is available and diagnostic for inoperable malignancy, we may perform EUS-guided neurolytic block at the time of the initial endoscopic evaluation. Early pancreatic cancer pain appears to derive mainly from the celiac plexus, while pain during the terminal stages of disease may also involve other visceral and somatic nerves. Thus, EUS-guided neurolysis performed soon after the onset of pain from pancreatic cancer may increase the rate of response. (See "Supportive care of the patient with locally advanced or metastatic exocrine pancreatic cancer", section on 'Pain'.)
Patient preparation — The preprocedure preparation for patients is similar to that described for patients undergoing upper gastrointestinal endoscopy (see "Overview of upper gastrointestinal endoscopy (esophagogastroduodenoscopy)", section on 'Patient preparation'):
●Adjusting anticoagulation medications – Most patients do not need to discontinue aspirin when undergoing EUS-guided celiac plexus interventions. While holding nonsteroidal anti-inflammatories (NSAIDs) is not required for all patients, NSAID management is typically guided by endoscopist preference.
The procedure-related bleeding risk for patients on anticoagulants and/or nonaspirin antiplatelet agents is high (table 1). The management of antiplatelet and anticoagulant therapy in patients undergoing endoscopy is typically individualized, managed in conjunction with the prescribing specialist, and is discussed separately. (See "Management of antiplatelet agents in patients undergoing endoscopic procedures" and "Management of anticoagulants in patients undergoing endoscopic procedures".)
●Intravenous hydration – Before the procedure, patients are hydrated with a crystalloid solution intravenously to minimize the risk of hypotension during or after the procedure. (See 'Intervention-related' below.)
The choice of fluid, volume of fluid, and timing of administration are individualized based on patient comorbidities (eg, congestive heart failure), preprocedure volume status, and anesthetic agent(s). Adverse effects of anesthetic agents (eg, propofol) and the approach to procedural fluid management is discussed separately. (See "Intraoperative fluid management" and "Anesthesia for gastrointestinal endoscopy in adults".)
●Anesthesia – The procedure is typically performed on an outpatient basis using monitored anesthesia care. Anesthesia for endoscopic procedures is discussed separately. (See "Anesthesia for gastrointestinal endoscopy in adults".)
Equipment — EUS is performed with an echoendoscope (an endoscope with an ultrasound transducer engineered into its tip). The curvilinear array echoendoscope provides a 180-degree view that is in the same plane as the shaft of the echoendoscope, thereby permitting real-time visualization of the needle as it is advanced into the periluminal space.
Choice of needle is based on endoscopist preference and needle availability, and no specific needle type or size has been proven superior. Needle options include (see "Endoscopic ultrasound-guided fine needle aspiration in the gastrointestinal tract", section on 'Equipment'):
●A fine needle aspiration (FNA) needle, ranging in size from 19- to 22-gauge. The 22-gauge FNA needle has been commonly used for celiac plexus interventions.
●A dedicated, 20-gauge celiac plexus needle with multiple side holes that facilitate spreading of the injected material.
Technique — Technique for celiac plexus intervention using EUS guidance is summarized as follows :
●Position the patient in the left lateral decubitus position.
●Advance the curvilinear array echoendoscope through the mouth to the posterior lesser curve of the fundus of the stomach to identify the aorta, which appears in a longitudinal plane (image 1).
●Trace the path of the aorta distally to the celiac trunk, which is the first major vessel branch below the diaphragm. Identify the celiac plexus, which is located anterior and lateral to the celiac trunk. With doppler imaging, confirm the vascular nature of the adjacent structures.
●Flush the needle with normal saline to remove air and then place it through the biopsy channel of the echoendoscope and into the stomach. Secure the needle to the hub of the channel.
●Using EUS guidance, direct the needle tip through the gastric wall and into the celiac region (5 to 10 mm along the lateral aspect of the aorta at the level of the celiac trunk origin) (figure 1 and image 2). For bilateral injection, begin by targeting the region to the right side of the celiac artery. We typically target the right side first because it is farther from the ultrasound transducer and more difficult to visualize than the left side.
●Flush the needle with 3 mL of normal saline to remove any tissue that was acquired during needle insertion. Arterial extension tubing attached to the needle can be used to facilitate flushing the needle with saline and the subsequent aspiration test.
●Prior to each drug injection, perform an aspiration test by applying suction to a 10 mL syringe for 15 seconds to confirm the absence of blood return.
●Inject a mixture of dehydrated alcohol USP (anhydrous ethanol for medical use, also known as absolute alcohol), 20 mL, and bupivacaine 0.25%, 4 mL, (ie, 5:1 ratio). This mixture can be placed in two 12 mL syringes (ie, one syringe for injecting each side of the celiac trunk). The alcohol produces an echogenic cloud and may lead to patient discomfort immediately following injection and resulting in patient movement, despite sedation/anesthesia (image 3).
The volume of alcohol in the injectate mixture varies among clinicians but typically ranges from 10 to 30 mL. Studies have not demonstrated a significant difference in symptom improvement with different volumes of injectate .
●After each drug injection, flush the needle with 3 mL of normal saline to ensure that the needle lumen is cleared of the drug(s). Seeding of the needle track with alcohol may produce transient but severe post-injection pain.
●Repeat the entire process on the opposite side of the celiac trunk.
●Before withdrawing the needle from the echoendoscope, flush it with normal saline 3 mL.
Options for technique modification include:
●Unilateral injection – For patients with bulky lymphadenopathy, a large pancreatic mass, and/or advanced cancer that results in altered anatomy, the procedure may be technically limited. For such patients, one injection may be performed on either the right or left side of the region surrounding the celiac artery.
Postprocedure care — After the procedure, patients are recovered from sedation or anesthesia and are monitored prior to discharge. (See "Anesthesia for gastrointestinal endoscopy in adults", section on 'Postanesthesia care'.)
Efficacy — Data from several trials and meta-analyses have reported that EUS-guided celiac plexus neurolysis was effective for alleviating pancreatic cancer pain in 50 to 80 percent of patients for approximately two to three months [6,10-13]. EUS-guided neurolysis is one method for managing pain from pancreatic cancer, while most patients require pharmacologic therapy (eg, opioids, nonsteroidal anti-inflammatory medications). The approach to pain management for patients with pancreatic cancer is discussed separately. (See "Supportive care of the patient with locally advanced or metastatic exocrine pancreatic cancer", section on 'Pain'.)
The neurolytic agent used during EUS-guided neurolysis induces a local inflammatory reaction, followed by fibrosis during the healing process .
For EUS-guided celiac plexus interventions, we typically use bilateral injection (ie, drug injection on both sides of the celiac artery) when technically feasible to optimize distribution of the injectate over the celiac plexus. However, data on drug injection placement have been mixed. In two meta-analyses, short-term pain relief was not significantly different for EUS-guided celiac plexus neurolysis with bilateral injection (ie, administering the injectate in two divided doses on each side of the root of the celiac artery) compared with unilateral injection (ie, injecting of the total volume immediately anteriorly to the root of the celiac artery) [11,15,16]. In a study including 160 patients, EUS-guided celiac plexus neurolytic or nonneurolytic block with bilateral injection was associated with greater reduction in pain compared with central injection (mean percent pain reduction: 70 versus 46 percent) .
Nonneurolytic block (celiac plexus block)
Patient selection — EUS-guided celiac plexus nonneurolytic block is typically used for short-term relief of abdominal pain in patients with chronic pancreatitis who require opioid analgesics or do not wish to use opioids. The nonneurolytic block typically involves injecting local anesthetic combined with a glucocorticoid into or around the celiac plexus. The management of chronic pancreatitis is discussed separately. (See "Chronic pancreatitis: Management".)
Procedure — The procedure for EUS-guided celiac plexus block, including patient preparation, equipment, technique, and postprocedure care, is similar to the procedure for EUS-guided neurolysis in addition to the following :
●Patient preparation – Antibiotic prophylaxis is given to patients receiving injection of a local anesthetic, with or without a glucocorticoid. The antibiotic regimen typically consists of a fluoroquinolone, similar to other interventional EUS procedures and as presented in the table (table 2). (See "Antibiotic prophylaxis for gastrointestinal endoscopic procedures", section on 'Endoscopic ultrasound'.)
●Technique – For celiac plexus nonneurolytic block, agents for injection typically are a local anesthetic (bupivacaine 0.25%), often combined with a glucocorticoid (triamcinolone suspension 40 mg/mL):
We use bilateral injection when technically possible to optimize distribution of the injectate over the plexus, although supporting data are lacking.
Efficacy — Celiac plexus nonneurolytic block is an option for treating intractable pain related to chronic pancreatitis. The injection of a local anesthetic often combined with a glucocorticoid into the celiac plexus interferes with the perception of pain by disrupting nerve transmission [18,19]. In a meta-analysis of six studies including 221 patients with chronic pancreatitis, EUS-guided celiac plexus block (local anesthetic plus glucocorticoid) was associated with alleviation of abdominal pain in 52 percent of patients . In a subsequent cohort study including 248 patients with chronic pancreatitis, EUS-guided celiac plexus block was associated with pain relief in 177 patients (76 percent) and the median duration of effect was 10 weeks . (See "Chronic pancreatitis: Management", section on 'Celiac plexus block'.)
ADVERSE EVENTS — EUS-guided neurolytic and nonneurolytic blocks are relatively safe procedures, but minor and major adverse events can occur. Some adverse events are due to the endoscopy itself, the procedural sedation, or the interventional procedure. In a systematic review of 20 studies including 661 patients who had EUS-guided neurolysis and 481 patients who had EUS-guided nonneurolytic block, the overall complication rate for neurolysis was 21 percent and for nonneurolytic block was 7 percent . Most adverse events were minor and self-limited (usually lasting <48 hours). For patients with celiac plexus neurolysis, the most common adverse events were related to sympathetic blockage (self-limited diarrhea in 7 percent of patients and transient hypotension in 4 percent of patients) . Major adverse events were rare and were reported in less than one percent of patients undergoing EUS-guided neurolysis or nonneurolytic block. (See 'Intervention-related' below.)
Endoscopy-related — Adverse events associated with EUS may be due to the upper gastrointestinal endoscopy itself (without intervention) and/or the associated sedation and anesthesia. These adverse events are discussed in more detail separately. (See "Adverse events related to procedural sedation for gastrointestinal endoscopy in adults" and "Overview of upper gastrointestinal endoscopy (esophagogastroduodenoscopy)", section on 'Complications'.)
Intervention-related — Reported adverse events of EUS-guided neurolytic and nonneurolytic blocks have included [20-22]:
●Hypotension (usually transient)
●Diarrhea (usually self-limited)
●Postprocedural pain/exacerbation of existing pain (usually lasting <48 hours) 
●Infection (abscess, empyema) (rare) [7,24,25]
●Bleeding (rare) 
●Paraplegia (rare) [26-29]
●Diaphragmatic paralysis (rare) 
●Ischemia (rare) [31,32]
Hypotension that occurs during the procedure or recovery phase is initially managed with intravenous hydration. Management of hemodynamic issues following anesthesia is discussed in more detail separately. (See "Cardiovascular problems in the post-anesthesia care unit (PACU)".)
Transient diarrhea and hypotension are common manifestations of the interruption of the sympathetic supply to the intestines and blood vessels that can occur following EUS-guided neurolytic or nonneurolytic blocks . The celiac plexus is a dense network of abdominal visceral afferent nerve fibers and sympathetic fibers of the splanchnic nerves. Thus, interruption of the plexus not only reduces pain transmission from the abdominal organs (pancreas, liver, stomach, kidney, small bowel, and colon) but can also result in a sympathetic blockade. Clinical manifestations of sympathetic blockade can include diarrhea and hypotension due to relatively unopposed visceral parasympathetic activity.
Paralysis and acute spinal cord ischemia have been rarely reported after celiac plexus neurolysis. Case reports suggested various causes of infarction of the L1/L2 vertebrae (eg, embolic occlusion of the lumbar arteries, needle injury, injection of alcohol into the Adamkiewicz artery) . However, very few cases of irreversible paraplegia have been reported .
OTHER EUS-GUIDED INTERVENTIONS
Celiac ganglia neurolytic block — Several studies have noted that the celiac ganglia can be visualized with EUS guidance in approximately 60 to 90 percent of patients. Thus, neurolytic block (neurolysis) can be performed by directly injecting material (local anesthetic, alcohol) into individual celiac ganglia [8,34-37].
After visualizing the celiac artery with EUS, the celiac ganglia typically are seen to the left of the celiac artery, between the aorta and left adrenal gland. The celiac ganglia are predominantly hypoechoic, oval or round structures with irregular margins, and ranging in diameter from 2 to 20 mm and in number from one to five (image 4) [8,38]. The ganglia are hypoechoic in contrast to the surrounding retroperitoneal fat and often display similar echogenicity to that of the left adrenal gland. Central echo-rich strands or foci are present, and hypoechoic thread-like structures can be seen arising from ganglia. These threads connect to the ganglia, or course along the anterior surface of the celiac trunk. Color doppler ultrasonography confirms little or no flow within these structures.
Procedure — All aspects of the procedure including patient preparation, equipment, and postprocedure care are similar to that of celiac plexus neurolysis, except for the following modifications (figure 2) (see 'Neurolytic block (celiac plexus neurolysis)' above):
●Advance the needle tip through the gastric wall and to a distance determined by ganglion size within the axis of the needle plane:
•For ganglion size <10 mm in diameter, insert the needle to the center of the ganglion.
•For ganglion size ≥10 mm in diameter, advance the needle tip to the deepest point within the ganglion.
●Inject a mixture of dehydrated alcohol USP (anhydrous ethanol for medical use, also known as absolute alcohol) and bupivacaine 0.25% (mixed in a 1:1 ratio) as the needle is slowly withdrawn from the ganglion; this results in a hyperechoic appearance. The volume of the drug mixture that is injected into each ganglion depends on ganglion size and typically ranges from 1 to 5 mL per ganglion.
●Repeat the injection while targeting all visualized ganglia.
Direct injection commonly results in enlargement of the ganglia (image 5). Intra-ganglia injection is typically accompanied by the immediate onset of pain, which manifests as an abrupt increase in patient movement, attempted verbalization, altered pulse and respiration despite monitored anesthesia care. These manifestations resolve within a few seconds after ganglia injection, and have been associated with improved therapeutic response .
Efficacy — Data on efficacy of celiac ganglia neurolysis are mixed. Small studies have suggested that direct injection of the celiac ganglia was associated with reduction in pain for patients with pancreatic cancer [35,39], however, a subsequent trial indicated that celiac ganglia neurolysis resulted in decreased survival without a pain control benefit . In a trial including 110 patients with unresectable pancreatic cancer, there was no significant difference in rates of pain response at 12 weeks or adverse events for celiac ganglia neurolysis compared with celiac plexus neurolysis. However, celiac ganglia neurolysis resulted in shorter survival time (5.6 versus 10.5 months; hazard ratio 1.49, 95% CI 1.02-2.19). However, in an earlier trial including 34 patients with pain related to abdominal cancer, EUS-guided celiac ganglia neurolysis was associated with higher rates of treatment response (74 versus 46 percent) and complete pain relief (50 versus 18 percent) compared with celiac plexus neurolysis . There was no significant difference with regard to duration of pain relief or adverse events.
Additional data from randomized controlled trials are needed to assess the outcomes of EUS-guided direct injection of celiac ganglia before it can be used routinely in clinical practice. The use of celiac ganglia neurolysis for pain management should be individualized based on factors such as severity of pain and response to pain medications and other interventions. (See "Supportive care of the patient with locally advanced or metastatic exocrine pancreatic cancer".)
Broad plexus neurolytic block — EUS-guided broad plexus neurolysis involves injecting the neurolytic agent at the level of the superior mesenteric artery (rather than the celiac artery), resulting in a broader distribution of neurolytic block. Broad plexus neurolytic block is typically used for patients without improvement in pain following celiac plexus neurolytic block. Limited data have suggested that broad plexus neurolysis was associated with improvement of cancer-related pain [41,42]. In an observational study including 112 patients with abdominal cancer-related pain, EUS guided broad plexus neurolysis was associated with good pain response (defined as decrease in pain score without additional opioid requirement) in 76 patients (68 percent) at four weeks .
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic pancreatitis and pancreatic exocrine insufficiency" and "Society guideline links: Cancer pain".)
SUMMARY AND RECOMMENDATIONS
●Anatomy of the celiac plexus – The celiac plexus is a dense network of nerves including sympathetic and parasympathetic efferent fibers and visceral sensory afferent fibers that innervate the upper abdominal organs. The celiac plexus mediates the sensation of pain from the pancreas and includes right and left ganglia that lie anterolateral to the aorta at the origin of the celiac trunk (ie, the first large vessel to branch from the aorta below the diaphragm). (See 'Anatomy of the celiac plexus' above.)
●Terminology – Endoscopic ultrasound (EUS)-guided celiac plexus interventions involve drug injections at the level of the celiac artery (see 'Terminology' above):
•Celiac plexus neurolysis (neurolytic block) – Celiac plexus neurolytic block is an intervention that permanently alters the affected nerve.
•Celiac plexus block (nonneurolytic block) – Celiac plexus nonneurolytic block is an intervention that interrupts nerve transmission without permanently injuring the affected nerve.
•Additional techniques – Celiac ganglia neurolysis (directly injecting the neurolytic agent at the celiac ganglia via EUS) and broad plexus neurolysis (injecting the neurolytic agent at the level of the superior mesenteric artery)
●Contraindications – There are few contraindications to EUS-guided celiac plexus interventions including hemodynamic instability, inability to tolerate anesthesia/sedation, and coagulation disorders. (See 'Contraindications' above.)
●Patient selection – Patients with inoperable cancer and abdominal pain requiring opioid analgesics (or patients with pain who do not wish to use opioids) are candidates for celiac plexus neurolysis (neurolysis). EUS-guided celiac plexus neurolysis produces analgesia by destroying afferent neural pathways or sympathetic structures involved in pain transmission.
Celiac plexus nonneurolytic block is an option for treating intractable pain related to chronic pancreatitis. The injection temporarily interferes with the perception of pain by disrupting nerve transmission. (See 'Patient selection' above.)
●Technique – The technical procedure of EUS-guided celiac plexus neurolysis includes identifying the celiac plexus, advancing the needle through the gastric wall and into the celiac region, flushing the needle with saline, applying suction to confirm absence of blood return, and injecting the drug, typically with a bilateral approach. For some patients with bulky lymphadenopathy or large pancreatic tumors, a unilateral approach for injection is an alternative. (See 'Technique' above.)
●Adverse events – EUS-guided celiac plexus interventions are generally safe procedures, and serious adverse events are infrequently reported. Transient diarrhea and hypotension are common manifestations of the sympathetic blockade that can occur following EUS-guided neurolytic or nonneurolytic blocks. Hypotension is managed with intravenous hydration before, during, and after the procedure. (See 'Adverse Events' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Michael Levy, MD (deceased), who contributed to earlier versions of this topic review.
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