Increasing the Efficacy of a Celiac Plexus Block in Patients with Severe Pancreatic Cancer Pain

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1 966 Journal of Pain and Symptom Management Vol. 22 No. 5 November 2001 Original Article Increasing the Efficacy of a Celiac Plexus Block in Patients with Severe Pancreatic Cancer Pain Jan H. Vranken, MD, Wouter W. A. Zuurmond, MD, PhD, and Jaap J. de Lange, MD, PhD Department of Anesthesiology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands Abstract The purpose of this study was to evaluate the technical possibilities of placing a catheter near the celiac plexus for performance of a celiac plexus block, and to study the efficacy of repeated neurolytic celiac plexus blocks with alcohol in patients with advanced pancreatic cancer pain resistant to opioid treatment. In 12 patients, a neurolytic celiac plexus block with alcohol, administered via an indwelling celiac catheter, was performed. To evaluate the efficacy, visual analog scale scores were recorded every day. Quality of life scores were registered before and 4 weeks following the procedure. Alterations in opioid consumption, and the time between the diagnosis of pancreatic cancer and the performance of the block, were registered. All patients were followed until they died. Two patients remained without pain after the first neurolytic celiac plexus block. In all other patients a second block was administered which provided only temporary relief. Additional intermittent administration of bupivacaine through the catheter was necessary to provide adequate pain relief in these patients. Quality of life increased significantly during the treatment. Opioid consumption decreased significantly in all patients. Our study indicates that a neurolytic celiac plexus blockade with alcohol results in a significant but short-lasting analgesic effect. The use of a celiac catheter improves the longterm management of pancreatic cancer pain. J Pain Symptom Manage 2001;22: U.S. Cancer Pain Relief Committee, Key Words Pancreatic pain, cancer pain, celiac plexus block, pain management, quality of life, catheter Address reprint requests to: Jan H. Vranken, MD, Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Accepted for publication: January 20, Introduction Pancreatic cancer causes pain characterized by progressively increasing severity. Pain occurs in 80% of patients and is often the dominant symptom at the time of diagnosis. 1 Furthermore, in an advanced stage of the disease, 90% of patients complain of significant pain. 2 Pancreatic cancer pain classically presents as a relentless mid-epigastric pain. Radiation through or around to the back is reported in 25%. 3 Since pancreatic cancer still has a very poor prognosis and causes severe pain, palliative care providing adequate pain relief should be the major goal in the treatment of these patients. 4 Pancreatic cancer pain is primarily relieved with pharmacological therapy including acet- U.S. Cancer Pain Relief Committee, /01/$ see front matter Published by Elsevier, New York, New York PII S (01)

2 Vol. 22 No. 5 November 2001 Celiac Catheter and Pancreatic Cancer Pain 967 aminophen (paracetamol), nonsteroidal antiinflammatory drugs (NSAIDs), adjuvant analgesics, and opioids. In addition to pharmacological therapy, the neurolytic celiac plexus block is claimed to be an effective approach in management of pancreatic cancer pain. 5 Although the neurolytic celiac plexus block was first described in 1914, 6 the effectiveness and the duration of the analgesic effect have not been evaluated thoroughly. 7 9 An indwelling catheter, percutaneously placed in the retroperitoneal space near the celiac plexus, enables the physician to perform a celiac plexus block with local anesthetics (prognostic) or alcohol (neurolytic). This celiac catheter can subsequently be used to repeat the celiac plexus block. 10,11 The purpose of the present study was to evaluate the technical possibility of placing the catheter and the efficacy of repeated celiac plexus blocks with alcohol or local anesthetics. The effects were assessed using a visual analog scale (VAS) and quality of life (QOL) questionnaires. Methods After approval by the local ethics committee, informed consent was obtained from all study patients. Twelve patients with pancreatic cancer, previously treated with standard chemotherapy in combination with radiation therapy, were included in this study. All patients suffered from mid-epigastric pain radiating to the back, which was not adequately relieved by either oral morphine or transdermal fentanyl. At the time of inclusion, tumor infiltration was limited to the pancreas and there was no evidence of metastatic spread (clinical or radiological). Measurements Pain intensity was measured before the placement of the celiac catheter and daily until the patient died using a VAS. Quality of life was evaluated before and 4 weeks after placement of the celiac catheter using the Medical Outcome Studies (MOS) 36-item Short Form Health survey (SF-36) 12 and the Dartmouth COOP Functional Health assessment, COOP/ WONCA Scale charts (COOP/WONCA). 13 The SF-36 survey includes 8 general health concepts: vitality, bodily pain (pain), general health perceptions (health), mental health (mental), social functioning (social), role limitation due to physical health problems (role), physical functioning (physical), and role limitation due to emotional problems (emotional). Registration of changes noticed by the patient (reported changes) are also recorded. In the COOP/WONCA, patients respond to 6 questions with answers ranging from poor (Score V) to excellent (Score I). The quantity of opioids was registered before the procedure and each day after the procedure until the end of treatment (patient s death). Technique With the patient in prone position, a 15-cm epidural needle (Tuohy, 18 G) was inserted 7.5 cm to the right of the midline at the level of the L1 spinous process, just beneath the 12th rib (Figure 1). 14 After confirmation of the correct position of the needle using contrast fluid and biplane fluoroscopy, a 20 G (Perifix, Braun) catheter was passed through the needle and placed near the celiac plexus (Figure 2). Subsequently, 40 ml of bupivacaine 0.25% was administered via the catheter. When sufficient pain relief occurred, the block was considered to be positive and the catheter was tunneled subcutaneously to the ventral side of the body and fixed to the skin with a transparent dressing (Tegaderm, 3M Health Care, Germany). A neurolytic celiac plexus block (NCPB) with 40 ml of alcohol 70%, administered via the celiac catheter was then performed. Blockade was defined as successful when the patient scored lower than 4 on the VAS. After reoccurrence of pain, defined as a VAS score greater than 4, a second NCPB was performed. Pain-free periods and reduction in analgesic therapy were recorded. Both NCPBs were performed after fluoroscopic confirmation of the position of the catheter. In patients with insufficient pain relief after the second NCPB, the catheter was used for administration of 20 ml of bupivacaine 0.25%, two times a day. In the hospital, patients were observed for hemodynamic instability. After discharge from the hospital, the patient s care was transferred to the general practitioner and the home nursing service. A family member who was trained in injection techniques performed the administration of bupivacaine via the catheter assisted by an experienced home nurse. One hour after the administration of bupivacaine, the family

3 968 Vranken et al. Vol. 22 No. 5 November 2001 Fig. 1. Landmarks needed to perform the blockade of the celiac plexus. The black arrowhead marks the cephalic portion of the L1 spine; the white arrowhead corresponds to the L2 vertebral body. Entry point of the needle (black arrow) is the intersection of the twelfth rib and the lateral border of the paraspinal muscles. Fig. 2. Celiac plexus block: lateral fluoroscopic view showing the spread of contrast fluid (black arrow) at L1 vertebral body. White arrow indicates the catheter.

4 Vol. 22 No. 5 November 2001 Celiac Catheter and Pancreatic Cancer Pain 969 member was asked to measure the blood pressure of the patient. When sufficient pain relief was reached (VAS score 4), the celiac catheter remained in situ until the patient s death. Side effects, due to the insertion of the catheter and performance of the NCPB, were recorded. Statistics The data are presented as mean SD, or median and range for nonparametric data. The SAS statistical program, version 6.12, was used for statistical analysis of continuous variables and ordered categorical variables. The VAS scores were analyzed using the Friedman test. The SF-36 was analyzed using the Wilcoxon test. The chi-square test was used for analysis of the COOP/WONCA. In all cases, P 0.05 was considered to be significant. Results Patient characteristics are displayed in Table 1. All patients suffered from severe pancreatic cancer pain, which was resistant to opioids. In addition, 6 patients experienced nausea and vomiting. In Table 2, opioid consumption before and after placement of the celiac catheter is described. Although there was a significant reduction in opioid consumption, only three patients experienced sufficient pain relief without opioids until the patient s death. All the other patients remained on an opioid-based treatment. The interval between diagnosis and treatment, results (pain relief), and the duration of the catheter treatment are shown in Table 3. The NCPB was performed at a mean interval of days (range: ) after diagnosis of the malignancy. Table 2 Daily Opioid Usage Before NCPB and on the Day Before Death (Steady-State) Patient Opioid dosage before procedure Opioid dosage in steady-state 1 Morphine SR 200 mg/d Tramadol 400 mg/d 2 Fentanyl TTS 350 g/h Fentanyl TTS 50 g/h 3 Fentanyl TTS 200 g/h Morphine SR 20 mg/d 4 Fentanyl TTS 150 g/h Paracetamol 2 g/d 5 Morphine SR 160 mg/d Morphine SR 20 mg/d 6 Morphine SR 600 mg/d Morphine SR 60 mg/d 7 Fentanyl TTS 100 g/h Fentanyl TTS 25 g/h 8 Morphine SR 300 mg/d Buprenorphine 1.2 mg 9 Fentanyl 100 g/h TTS Diclofenac 150 mg/d 10 Fentanyl 450 g/h TTS Paracetamol 3 g/d 11 Fentanyl 600 g/h TTS Fentanyl 25 g/h TTS 12 Fentanyl TTS 150 g/h Fentanyl 25 g/h TTS TTS transdermal therapeutic system; SR slow release. The prognostic block with 40 ml of bupivacaine 0.25% was successful in all patients, with a mean period of analgesia of 0.7 days (range: 0.4 1). Permanent pain relief after the first administration of alcohol was achieved in 2 out of 12 patients. In the other 10 patients, a second dose of alcohol was needed, after an average period of 25 days (range: 1 63). In these 10 patients, the mean time of analgesia after the second NCPB lasted for 10.1 days (range: 2 21). Subsequently, bupivacaine 0.25% was administered intermittently until the patients death. The VAS scores for each patient during treatment are shown in Figure 3. The VAS score decreased significantly after each administration of local anesthetic or alcohol. The VAS score increased significantly on the day the patient died. Quality of life measurements, before and 4 weeks after placement of the celiac plexus Table 1 Pancreatic Cancer Patient Data Patient Bodyweight (kg) Age (y) Sex Indication f Pain f Pain m Pain, nausea, vomiting f Pain, nausea, vomiting f Pain, nausea, vomiting f Pain m Pain, nausea, vomiting m Pain m Pain m Pain, nausea, vomiting m Pain, nausea, vomiting m Pain Mean SD

5 970 Vranken et al. Vol. 22 No. 5 November 2001 Patient Table 3 Interval Between Diagnosis and Treatment, and Summary of Pain Relief in the 12 Patients Time interval (days) Pain relief after bupivacaine 100 mg (days) Pain relief after first NCPB (days) Pain relief after second NCPB (days) Bupivacaine 2 50 mg/d Duration of catheter treatment (days) Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Not necessary Not necessary Not necessary Not necessary 63 Mean SD catheter, are shown in Figures 4 and 5. The QOL could not be assessed in one patient (patient 10 died 10 days after start of the treatment). On the SF-36, physical functioning increased and bodily pain decreased significantly. All the other parameters did not change significantly (Figure 4). On the COOP/WONCA questionnaire, there was a significant change in answers from the higher scores (Score V: poor quality of life) to the lower scores (Score I: excellent quality of life), suggesting a significant improvement in the quality of life (Figure 5). Although some patients experienced some minor adverse events such as orthostatic hypotension, diarrhea, and backache following celiac plexus block, no additional treatment was necessary. At home, no hemodynamic instability following administration of bupivacaine via the catheter was observed. Discussion Pancreatic cancer pain is primarily treated by the combination of NSAIDs, adjuvant analgesic drugs and oral or transdermal opioids. 3 The percutaneous NCPB has been recommended as adjuvant therapy for the treatment of pancreatic cancer pain. 15,16 In a meta-analysis, it was shown that the NCPB had a shortterm analgesic effect in 85% of the cases. 8 Studies evaluating the long-term effects are rather controversial due to inconsistencies and deficiencies in the assessment of the results. 7,17 Theoretically, tumor growth, nerve recruitment, or nerve regeneration within the celiac plexus may be responsible for the reappearance of pain in the upper visceral region after an NCPB. 7 If this were true, an NCPB should diminish the pain once again. However, the results of repeated NCPBs are disappointing. 5 In the present study, a catheter was placed near the celiac plexus for the administration of neurolytic agents or local anesthetics. 11,12 The correct placement of the catheter was verified by the administration of contrast fluid and biplane fluoroscopy. A prognostic block with bupivacaine was followed by a pain-free period. Subsequently, all patients received alcohol administered via the catheter. In 2 out of 12 patients, a single NCPB was effective until the patient died (Figure 3, Patients 11 and 12). In all the other patients, the analgesic effect was extended by a second celiac plexus block with alcohol. Since pain relief was temporary, a local anesthetic with a less toxic profile was subsequently used to obtain a continuous celiac plexus block. These patients remained also without pain until they died. Instead of bolus administration (20 ml of bupivacaine 0.25%, twice a day), a continuous infusion with bupivacaine using an external delivery system is a valuable alternative. These external delivery systems are small enough to allow walking. The main disadvantage is that the patient is connected with a pump and technical failure or catheter disconnection can occur, resulting in poor analgesia. 18 On the day of death, there was a significant increase in the VAS scores. Although the explanation for this event is speculative, increase in

6 Vol. 22 No. 5 November 2001 Celiac Catheter and Pancreatic Cancer Pain 971 Fig. 3. VAS plotted against time (in days) during the treatment with an indwelling celiac catheter. All patients received 40 ml of bupivacaine 0.25% on day 0. *First NCPB; **Second NCPB; ***Intermittent administration of 20 ml bupivacaine 0.25%.

7 972 Vranken et al. Vol. 22 No. 5 November 2001 Fig. 3. Continued

8 Vol. 22 No. 5 November 2001 Celiac Catheter and Pancreatic Cancer Pain 973 Fig. 3. Continued pain in the last days of a terminal illness, especially cancer, can be attributed to organic brain disease consequent to metabolic disorder associated with multi-organ failure. 19 The disappointing long-term results of a NCPB with alcohol in the present study cannot be explained in terms of misplacement of the celiac catheter or tumor metastases. All pa-

9 974 Vranken et al. Vol. 22 No. 5 November 2001 Fig. 3. Continued tients eventually experienced sufficient pain relief until they died after either administration of alcohol or administration of alcohol followed by intermittent administration of a local anesthetic via the catheter. One of the advantages of this technique is the possibility for the administration of neurolytic and local anesthetic agents. If sufficient pain relief is ob-

10 Vol. 22 No. 5 November 2001 Celiac Catheter and Pancreatic Cancer Pain 975 Fig. 4. Results of the SF-36 survey (median and range). There was a significant decrease in pain and a significant increase in physical functioning; (*P 0.05). tained after the administration of a local anesthetic, a NCPB with alcohol can be performed. In contrast to a single shot NCPB, this technique avoids a needless neurolytic procedure and prevents complications related to the use of alcohol. Furthermore, the application of this technique resulted in a significant improvement in pain relief according to the VAS trend in all patients participating in this study. The quality of life (functional and physical Fig. 5. COOP/WONCA scores. There was a significant improvement in the COOP/WONCA scores 4 weeks after treatment. The figures are the number of recorded answers (y axis). The patient could choose between 5 answers (I best, V worst; x axis).

11 976 Vranken et al. Vol. 22 No. 5 November 2001 health in particular) increased significantly after this treatment. Obviously, it seems unlikely that other parameters, such as mental health, role functioning, and social functioning, would improve as a consequence of adequate pain relief. 20 In the study performed by Kawamata et al., no improvement was found on the QOL after single shot NCPB with alcohol. 4 Limitations of this technique are clear. In advanced tumor infiltration and metastatic spread, pancreatic cancer pain becomes multifactorial and multiple pain mechanisms and pathways (somatic, neuropathic, and visceral) must be considered. 21 A celiac plexus block is only effective in controlling visceral cancer pain and should be considered as important adjunct to pharmacological therapy. 22 In this study, the total need for opioids could be significantly reduced after performance of the celiac plexus block in all patients. Nine patients were still treated with opioids to relieve non-visceral pain. However, should pain relief still fail after the combination of pharmacological therapy with a neurolytic celiac plexus block, analgesia provided by spinal analgesics should be considered. The incidence of major complications associated with the performance of a neurolytic celiac plexus block such as retroperitoneal hemorrhage, abdominal aortic dissection, and paraplegia is very low and did not occur in this study. 7 No additional side effects inherent to the use of a catheter were recorded. 23 Based on our results, we conclude that the performance of a celiac plexus block using a catheter increases the safety of this blockade by avoiding administration of alcohol in those patients without pain relief after a diagnostic block with local anesthetics. A celiac catheter can be used for either repeated instillation of alcohol or intermittent administration of local anesthetics in the celiac plexus to achieve sufficient pain relief until the patient dies. Our results are promising and a randomized trial has to be performed to compare the efficacy of a single shot NCPB versus an NCPB using a catheter. References 1. Salzburg D, Foley KM. Management of pain in pancreatic cancer. Surg Clin North Am 1989;69: Foley KM. Pain syndromes and pharmacological management of pancreatic cancer pain. J Pain Symptom Manage 1988;3: Lebovits AH, Lefkowitz M. Pain management of pancreatic carcinoma: a review. Pain 1989;36: Kawamata M, Ishitani K, Ishikawa K, et al. Comparison between celiac plexus block and morphine treatment on quality of life in patients with pancreatic cancer pain. Pain 1996;64: Brown DL, Bulley CK, Quiel EC. Neurolytic celiac plexus block for pancreatic cancer pain. Anesth Analg 1987;66: Kappis M. Erfahrungen mit localanasthesie beim bauchoperationen. Verh Dtsch Gesellsch Chir 1914;43: Mercadante S, Nicosia F. Celiac plexus block. A reappraisal. Reg Anesth Pain Med 1998;23: Ischia S, Ischia A, Polati E, Finco G. Three posterior percutaneous celiac plexus block techniques. Anesthesiology 1992;76: Eisenberg E, Carr DB, Chalmers TC. Neurolytic celiac plexus block for treatment of cancer pain: a meta-analysis. Anesth Analg 1995;80: Rykowski JJ, Hilgier M. Continuous celiac plexus block in acute pancreatitis. Reg Anesth 1995; 20: Hilgier M, Rykowski JJ. One needle transcrural celiac plexus block. Single shot or continuous technique, or both. Reg Anesth 1994;19: McHorney CA, Ware JE, Lu JF, Sherbourne CD. The MOS 36-item Short-Form Health survey (SF- 36): III. Tests of data quality, scaling assumptions and reliability across diverse patients groups. Med Care 1994;32: Nelson EC, Wasson J, Kirk J. Assessment of function in routine clinical practice. Description of the COOP chart method and preliminary findings. J Chron Dis 1987;40: Kopacz DJ, Thompson GE. Celiac and hypogastric plexus, intercostal, interpleural, and peripheral neural blockade of the thorax and abdomen. In: Cousins MJ, Bridenbaugh PO, eds. Neural blockade in clinical anesthesia and management of pain, vol 3. Philadelphia: Lippincott-Raven, 1998: Moore DC. Celiac (splanchnic) plexus block with alcohol for cancer pain of the upper intraabdominal viscera. In: Bonica JJ, Ventafridda V, eds. Advances in pain research and therapy, vol 2. New York: Raven, 1979: Mercadante S. Celiac plexus block versus analgesics in pancreatic cancer pain. Pain 1993;52: Polati E, Finco G, Gottin L, et al. Prospective randomized double-blind trial of neurolytic celiac plexus block in patients with pancreatic cancer. Br J Surg 1998;85: Mercadante S. Controversies over spinal treat-

12 Vol. 22 No. 5 November 2001 Celiac Catheter and Pancreatic Cancer Pain 977 ment in advanced cancer patients. Support Care Cancer 1998;6: Lichter I, Hunt E. The last 48 hours of life. J Palliat Care 1990;6: Thomas EM, Weiss SM. Nonpharmacological interventions with chronic cancer pain in adults. Cancer Control 2000;7: Rykowski JJ, Hilgier M. Efficacy of neurolytic celiac plexus block in varying locations of pancreatic cancer. Anesthesiology 2000;92: de Leon-Casasola OA. Critical evaluation of chemical neurolysis of the sympathetic axis for cancer pain. Cancer Control 2000;7: Boersma FP, Blaak HB, Ten Kate-Ananias A, Zuurmond WWA. Technical complication and sequelae of long-term epidural cancer pain control: a review of 206 cases. Pain Clinic 1993;6: