Computed tomography versus fluoroscopy guidance in celiac plexus neurolysis for treatment of upper abdominal malignant pain

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1 Computed tomography versus fluoroscopy guidance in celiac plexus neurolysis for treatment of upper abdominal malignant pain Thesis Submitted for the partial fulfillment of MD Degree in anesthesiology and pain relief Presented by Suzan Adlan Abdelrahman (M.B.B.Ch & M Sc.) Under Supervision of Professor Dr. khaled Abdelhameed Moustafa Professor of anesthesiology and pain relief National Cancer Institute Cairo University Professor Dr. Ikram Hamed Mahmoud professor of Radiodiagnosis National Cancer Institute Cairo University Dr. Azza fouad omran Assistant professor of anesthesiology and pain relief National Cancer Institute Cairo University Dr. Ahmed Shaker Ragab Lecturer of anesthesiology and pain relief National Cancer Institute Cairo University

2 National Cancer Institute Cairo University 2015 INTRODUCTION AND AIM OF THE STUDY Introduction Despite advances in pain management, pain remains a common persistent symptom among persons with cancer.estimates of pain prevalence among persons with cancer range from 14%-100% (Patrick et al; 2002). In a population-based study, vanden Beuken-van Everdingen et al. concluded that pain control remains inadequate in 42% of patients, especially among those receiving curative cancer therapies (vanden Beuken-van Everdingen et al; 2007). Given et al. found pain was most likely to occur within 40 days of receiving surgery, chemotherapy or radiation. Patients presenting with pain tend to have more advanced disease and thus, more other symptoms (Given et al; 2001). The effect of the sympathetic nervous system as a factor in a variety of painful conditions in humans has been a part of conventional medical wisdom for over 100 years. The sympathetic nervous system (SNS) is a part of the autonomic nervous system that controls the body s involuntary activities. It has been implicated in neuropathic pain (NeP), vascular, and visceral pain. Sympathetic ganglia have been the target of local anaesthetic block to assess the role of the SNS in transmission of pain. Despite the frequent use of minimally invasive sympathetic blocks by pain practitioners, their efficacy for providing analgesia has been sparsely reported. Many case reports and series have been published, but few placebo-controlled, blinded studies exist. Sympatholysis may be performed with local anaesthetics, neurolytics, and neuroablative techniques such as radiofrequency lesioning (Day, 2008). To block a sympathic nerve, we inject the local anesthetic onto the sympathetic chain at various sites. The primary sympathetic ganglia involved in pain include the stellate ganglion, the celiac plexus, the lumbar sympathetic ganglion, the superior hypogastric plexus, and the ganglion impar. Visceral cancer pain from upper abdominal viscera (pancreas, liver, gall bladder and stomach) may be abolished by a neurolytic celiac plexus block (NCPB).The celiac sympathetic ganglia are located on

3 both sides of the celiac artery anterior to the aorta and anterior to the crura of the diaphragms (Erdine, 2005). Malignant tumors originated from pancreas, stomach and liver may cause abdominal pain which is unresponsive to large doses of narcotic analgesics and which considerably impairs the patient's quality of life. Coeliac plexus block (CPB) has been used as adjunct therapy in such cases (Edrine, 2005). Before the 1970s, celiac plexus blocks were performed blindly, in 1979; Hegedus stressed the importance of using radiological guidance to locate the exact level of the celiac axis. Celiac plexus block can be performed with imaging techniques such as fluoroscopy, CT, MRI, ultrasound and endoscopicultrasound (Yang and Oraee, 2005). Pain practitioners have to rely on fluoroscopy for image-guided injection for an increasing number of analgesic procedures. Although fluoroscopy can provide multiplanar visualization of a needle or instrument it is incapable of directly visualizing soft tissue abnormalities. Fluoroscopic localization of instruments depends on indirect information obtained from displacement of contrast filled structures (John et al; 2009). Computed tomography (CT) represents at present the best imaging guidance technique in numerous interventional procedures. Owing to the high spatial resolution and the good tissue contrast, it is possible to place precisely and safely needle and trocar tips on target, and lytic agents or antiinflammatory drugs can be delivered with high reliability. This result in significantly reduced morbidity (lower than 2.5% out of 756 interventions) and improves the effectiveness of the various interventional procedures (Kastler et al, 2001). In certain procedures where real-time imaging is necessary a combination of CT and X-ray fluoroscopy may be interesting (Gangi et al, 1994). One of the concerns with the use of CT fluoroscopy is the high radiation exposure (Nawfel et al; 2000). In contrast with conventional fluoroscopy in which the patient dose is on the order of centigrays per minute of exposure, with CT fluoroscopy, patient doses may be on the order of centigrays per second. An additional concern is the scattered exposure to the hands and body of radiologists, since they may be close to the x-ray source during the manipulation of the needle (Kato et al; 1996). Abstract: Background: Visceral cancer pain from upper abdominal viscera (pancreas, liver, gall bladder and stomach) may be abolished by a neurolytic celiac plexus block (NCPB).The purpose of this study is to highlight differences between two techniques as regard efficacy by means of visual analogue scale (VAS), percent reduction in daily morphine consumption.

4 Methods: 60 patients with pancreatic cancer pain for which pharmacological treatment (NSAIDs and opioids) proved either ineffective or limited by side effects were randomly allocated into two groups. Study was done over eighteen months from January 2013 to June Each patient is assessed by linear visual analogue scale (VAS) and percent reduction in daily morphine consumption. All evaluation parameters were done before the block, at day (0) 2hr post block, 2 days, 2 weeks and 3 weeks post block. Results: the parameters were comparable with no significance difference between both techniques (Pvalue 0.05). Conclusion: We concluded that an effective NCPB, regardless of the technique used, produce immediate analgesia and allowed a reduction in opioid dose. AIM OF THE STUDY To evaluate two different techniques of coeliac plexus block, the first is done computed tomography guided and the latter is done under fluoroscopic guidance. All selected patients for both techniques are on pharmacotherapy with inadequate pain relief. To highlight differences between two techniques as regard efficacy by means of visual analogue scale (VAS), percent reduction in daily morphine consumption. Time of doing each technique from its beginning to the end. Any complications will be recorded and assessed. Review of Literature Anatomy of celiac plexus the largest of the three sympathetic plexuses is about 3 cm in length and 4 cm in width, typically lies anteriorly and anterolaterally to the aorta at the level between the T12-L1 intervertebral disc and L2 vertebral body. The ganglia located on the left are uniformly more inferior than their right-sided counter parts by as much as a vertebral level, but both groups of ganglia lie below the level of the celiac artery. The ganglia usually lie about at the level of the first lumbar vertebra. VISCERAL PAIN Visceral pain is the most common form of pain produced by disease and one of the most frequent reasons why patients seek medical attention. Yet much of what we know about the mechanisms of pain derives from experimental studies of somatic not visceral nociception. The conventional view is that visceral pain is simply a variant of somatic pain, a view based on the belief that a single neurological

5 mechanism is responsible for all pain. However, the more we learn about the mechanisms of somatic and visceral pain, the more we realise that although these two processes have much in common, they also have important differences. DIFFERENT TECHNIQUES OF CELIAC PLEXUSE BLOCK Celiac plexus block has been performed by an anterior or posterior approach Posterior (Classic, Retrocrural) Approach The patient is placed in the prone position with a pillow beneath the abdomen to reverse the thoracolumbar lordosis.this position increases the distance between the costal margins and the iliac crests and between the transverse processes of adjacent vertebral bodies. The operative field is prepared and draped in standard aseptic manner. Once the patient is positioned appropriately, a fluoroscopic view is taken in a Poster-Anterior (PA) position. Then The T12 vertebral body is identified with fluoroscopy (Waldman, 2015). The skin, subcutaneous tissues, and musculature are infiltrated with 1.0% lidocaine at the points of needle entry. Twenty-gauge, 13-cm styletted needles are inserted bilaterally through the previously anesthetized area. The needles are initially oriented 45 degrees toward the midline and about 20 degrees cephalad and are advanced under continuous fluoroscopic guidance to ensure contact with the inferolateral portion of the T12 vertebral body once bony contact is made with the T12 vertebral body and the depth is noted, the needles are withdrawn to the level of the subcutaneous tissue and redirected slightly less mesiad (about 60 degrees from the midline) and advanced under continuous fluoroscopic guidance so as to walk off the lateral surface of the T12 vertebral body. As the needles slide past the lateral surface of the vertebral body, the left-sided needle is gradually advanced approximately 1.5 cm under continuous lateral fluoroscopic guidance until the needle tip is resting at the anterior margin of the vertebral body of T12 (Fig.7).The right-sided needle is then advanced slightly farther(i.e., 2 cm past contact with the bone). Ultimately, the tips of the needles should be just anterior to the lateral border of the vertebral body and just behind the aorta and vena cava in the retrocrural space (Waldman, 2015). The stylets of the needles are then removed, and the needle hubs are inspected for the presence of blood, cerebrospinal fluid, or urine. After gentle aspiration a small amount of contrast material suitable for intrathecal use is injected through each needle, and its spread is observed radiographically. On the fluoroscopic anteroposterior view, contrast should be confined to the midline and concentrated near the T12 vertebral body (Fig.6). A smooth posterior contour should be observed that corresponds to the psoas fascia on the lateral view (Waldman, 2015). CT guided Bilateral Posterior Paravertebral Antecrural Approach

6 With this approach, the neurolytic agent is injected into the antecrural space by placing needles on each side by way of a posterior paravertebral route (Fig.12). Patients may be either in the prone or lateral decubitus position. Preliminary unenhanced abdominal CT is performed to help (a) localize the celiac artery and celiac plexus, (b) select the puncture site, (c) determine the angle and depth of needle entry, (d) identify the percutaneous needle path to the celiac plexus, and (e) determine the site of neurolytic agent injection. The optimal site of injection is the axial CT section located between the celiac trunk and the superior mesenteric artery (SMA) (Eisenberg et al; 1995). The skin at the point of needle entry is cleaned with antiseptic solution, and a sterile field is prepared. After subcutaneous infiltration with 1% lidocaine, a gauge bevel-tipped needle (Chiba needle is advanced alongside the vertebral bodies into the antecrural space, taking care to avoid the rib, transverse process, vertebral body, kidneys, and major vascular structures (Eisenberg et al; 1995). The ideal needle tip position is approximately 1 2 cm anterior to the aorta, between the diaphragmatic crura and the pancreas, at the level between the celiac trunk and the SMA. After the position of the needle tip is confirmed at CT, it is important to aspirate the needle to determine if blood is present (Eisenberg et al; 1995).If blood return is seen, the needle must be repositioned. If no blood return is seen, 5 ml of diluted iodinated contrast material is injected into the antecrural space (Thomson et al; 1987). A correct needle position at the initial contrast material administration is indicated by the presence of free diffusion of contrast material in the antecrural space at CT and no reports by the patient of numbness or motor dysfunction in the lower extremities. After free diffusion of contrast material is documented, approximately 40 ml (20 ml on each side) of absolute ethanol (95% 100%) is injected through the needle and into the antecrural space (Eisenberg et al; 1995). Transdiscal approach Transaortic Approach Bilateral Posterior Paravertebral Antecrural Approach Anterior Approaches to Celiac Plexus Block Endoscopic US guided celiac plexus neurolysis ABDOMINAL PAIN ASSESSMENT Visual Analogue Scale The visual analogue scale is a line, the length of which is taken to represent the continuum of some experience like pain. It is a simple, robust, sensitive, and reproducible instrument that enables a patient to express the severity of his pain in such a way that it can be given a numerical value. It has been useful for studies of pain severity in different groups of patients and particularly in clinical trials. Visual analogue scales can be used to compare pain severity in the same patient at different times or in groups of patients receiving different treatments. The design of a scale may profoundly affect its performance. Problems with visual analogue scales include failure to understand the concept, variation in

7 reproducibility along the length of the line, and doubts about the relationship of the measurement to the true pain experience. Nevertheless, visual analogue scales are widely used and very useful. CHEMICAL NEUROLYSIS Numerous different chemical substances and physical techniques have been applied to elements of the central and peripheral nervous systems in efforts to disrupt pain transmission in a durable yet safe fashion. Chemical neurolysis is a modality that has been used for pain control for almost a century. Multiple agents have been evaluated through the years, but only a few are still clinically relevant. A LCOHOL PHENOL GLYCEROL PATHOPHYSIOLOGY OF NEUROLYSIS Chemical and physical agents have a final common path way in their action on the nerve cells. They are employed with the aim of producing nerve injury sufficient to result in degeneration of the nerve fiber distal to the lesion along with its myelin sheath. This process is called Wallerian degeneration. This temporarily interferes with nerve cell transmission and thus results in nociceptive block. This type of degeneration does not completely dis rupt the nerve cell; persistence of the basal lamina of the Schwann cells potentially allows for axonal regrowth with reconnection to the proximal end of the nerve fiber. If, however, the nerve is surgically cut, there is com plete disruption of the neuron and basal lamina. This is more likely to result in disorganized regrowth without reconnection of the cut nerve endings, possibly result ing in production of painful neuromata and dysesthetic pain. This difference justifies reliance on the use of neurolytic agents over surgical interruption of peripheral nerve fibers for the treatment of chronic pain. MATERIALS AND METHODS (I) Selection of the patients The following materials and methods were applied to this Randomized Controlled Trial (RCT) with approval from the Ethics Committee at National Cancer Institute, Cairo University. This study was carried on sixty patients with pancreatic cancer pain from pain clinic of the National Cancer Institute, Cairo University. Study was done over eighteen months from January 2013 to June All patients were given information on the procedure and its possible complications, and written informed consent was obtained.

8 Patients were referred from surgery, medical oncology or radiotherapy departments. Diagnosis of pancreatic cancer pain was done in pain clinic. Primary diagnosis of malignancy was done in referring departments. Patients presented with constant and intractable dull aching upper abdominal pain regarded as celiac ganglion origin cancer radiating to back for which pharmacological treatment (NSAIDs and opioids) proved either ineffective or limited by side effects. Patients were randomly allocated to two groups using closed envelope for randomization. Group one: CT group (30 patients, scheduled for Neurolytic Celiac Plexus tomography guidance. Block (NCPB) by computed Group two: C-arm fluoroscopy group (30 patients, scheduled for Neurolytic Celiac Plexus Block (NCPB) by C-arm fluoroscopic guidance (control group) Patients were interviewed before the celiac plexus block (CPB) procedure to score using visual analog scale (VAS). obtain a baseline pain Inclusion criteria: -Patients with upper abdominal cancer pain (cancer pancreas). -Age of patients from years. Exclusion criteria: -Refusal of the patient. -Mentally retarded patients. -Uncorrectable coagulopathy (anticoagulant therapy, and hemorrhagic disorders) -Local infection or neoplasm can spread when needles are inserted through infected or cancerous tissues. - Bowel obstruction.

9 Investigations Before the procedure, all patients were evaluated with respect to their systemic diseases and hematological investigations (CBC, platelet function and prothrombin time). Also, CT scan was evaluated for tumor spread, any displacement or variation of anatomical structures. Preparation of the Patients Patients had 1000cc lactated Ringer solution via 18G intravenous catheter prior to the procedure. The vital parameters of the patients (heart rate, noninvasive blood pressure, and oxygen saturation) were monitored during and two hour after the procedure continuously. The patients were sedated preoperatively with midazolam 1-2mg. (II) Celiac plexus block Techniques used: The celiac plexus block was done by one of the following techniques: Group one: CT guided Bilateral Posterior Paravertebral Antecrural Approach Group two: Fluoroscopic guided Bilateral Posterior Paravertebral Antecrural Approach A 40-ml volume of 50%alcohol was used (20-ml on each side) for neurolytic block (Waldman, 2015). After the neurolytic solution is injected, each needle should be flushed with sterile saline solution, it is imperative that both needles be placed medially against the vertebral body to reduce the incidence of pneumothorax. Evaluating parameters: Each patient is assessed by linear visual analogue scale (VAS) (where 0 = no pain and 10 = worst pain imaginable), percent reduction in daily morphine consumption and Time of the procedure estimated from entrance of the patient to operative room to discharge of patient to PACU in minutes. All evaluation parameters were done before the block, at day 0 2hr post block, 2 days, 2 weeks and 3 weeks post block. All patients were observed during the whole period of study and the main side effects occurred were recorded in each group. Statistical analysis: Data was analyzed using SPSS package version 17. Numerical data were expressed as mean±sd and median (range). Qualitative data were expressed as frequency and percentage. For quantitative data, comparison between two groups was done using student t-test. ANOVA test for repeated measures was used to compare VAS score readings upon time. Correlation between numerical values was tested using Pearson method. P-value less than 0.05 were considered significant and power for the study set at 85%. This study was designed to compare the effectiveness of CT and fluoroscopic technique in antecrural approach; sixty patients were randomly selected from the pain clinic of the National Cancer Institute suffering from pancreatic cancer pain. We divided them into two equal groups. We performed NCPB

10 antecrural approach CT guided in group (I) and NCPB antecrural approach fluoroscopy guided in group (II). We used alcohol 50% and we injected the same volume of the neurolytic. We chose alcohol because of its better diffusability, longer duration of block, and less affinity for vascular structures than phenol. During the block we used only propofol increments and subcutaneous infiltration of the skin with lidocaine 1%. This favors complete recovery of the patient after two hours. We avoided the use of fentanyl making the block the only way of analgesia in the patient. We compared the VAS immediately preblock, two hours, three days, two weeks and three weeks postblock, reduction in daily morphine consumption, complications and time of the block. We found that no significant difference between both groups in VAS, reduction in daily analgesic consumption and complications. But, there is a significant difference between both groups in time of the block with p- value less than The mean values of VAS were very low by both techniques and throughout the period of observation after the block. Also, there is reduction in daily morphine consumption. In a meta-analysis of neurolytic, CPB for cancer pain it was concluded that the procedures carried out with fluoroscopy versus CT or ultrasound guided technique fail to show higher rates of success or lower incidence of adverse effects (Eisenberg et al; 1995). Neurolytic CPB is associated with both minor and major complications, minor complications are temporary and mild, and fortunately, major complications are usually rare (Naveira et al; 1996). In this study no serious complications occurred but minor complications were reported. Minor complications of CPB include temporary orthostatic hypotension, diarrhea and local pain. Up to 23% (7 patients) had transient orthostatic hypotension in CT group while, in flouroscopy group, 20% (6 patients) had transient orthostatic hypotension. Orthostatic hypotension is caused by loss of sympathetic tone and splanchnic vessels vasodilatation after CPB. It can be cured by intravenous infusion of fluids (Marcy et al; 2001). As regard diarrhea 30% (6 patients) had transient mild diarrhea in CT guided CPB. While, 25% (5 patients) fluoroscopy guided CPB had transient mild diarrhea. Patients report diarrhea due to sympathetic blockade and unopposed parasympathetic efferent influence after CPB, which usually resolves within 48 hr (Lee, 2000). Transient local pain in group CT guided CPB, 16.7% (5 patients) had back pain. While, in fluoroscopy guided group, 23% (7 patients) had back pain. The previous minor complications which occurred had no statistical significance in both procedures. There were no major technical complications noted in the study as paraplegia, pneumothorax, hematoma formation or kidney puncture.

11 The incidence of major complications associated with the performance of a neurolytic CPB such as retropritoneal hemorrhage, aortic dissection, pneumothorax, chylothorax, renal hematoma with hematurria, gastroparesis, diaphragmatic paralysis and paraplegia (Fitzgibbon et al; 2001).