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Interpleural analgesia for the treatment of severe cancer pain in terminally ill patients
Vol. 8 No. 7 October 1993
Journal ofPain and Symptom Management
505
David P. Myers, MD, MarkJ. Lema, MD, Oscar A. de Leon-Casasola, MD, and Douglas R. Bacon, MD Bejwtmtwt ofAnesthesioloa und Critical Care Medicine, Roswell Park Cancer Institute, and State University of New Yortiat BuflaLo School of Medicine, Buffalo, New Ymk
Interpleural analpia was used to alleviate acute, severe exacerbations of chronic pain unrelieved bq’pharmacologic therapy in ten terminal& ill cancerpatients. Pain from mPta.static disease to the neck, arms, chest, brachial plexus, thorax, or abdomen was effectivel_yeliminated between 7 hr and 40 o@s in nine patients, who died with minimal or no pain. The technique was pe@med fiSrna+ using bupivacaine. No side effects were detected. Interpleural analgesia appears to be effective in rapidly controlling acute exacerbations of cancer pain in terminally ill patients. Mcrreover, it may also be a suitable thapy for moribund patients when used as a continuous-infK$ion tpchnique. J Pain Symptom Manage 1993;8:505-510.
Chronic pain, cancer
pain, terminally ill, in&$&Ural analgesia
Recent reports have suggested that interpleural analgesia (IPA) may be of long-term benefit to patients suffering from extrapleural pain Fyndromes. 1-4 Durrani and colleagues’ and Ahlburg and colleagues4 alleviated severe pancreatic pain with interpleural bupivacaine, and Fineman found it useful in treating postthoracotomy pain syndromes. Johnson and colleagues,” Sihota and Holmblad,7 and Reiestad and colleaguesX used this technique to treat acute herpes zoster and postherpetic neural-
Address ybrint requests to: Mark J.
Lema, MD, Department of Anesthesiology and Pain Medicine, Roswll Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 142630001, USA. Acceptedfor publication: May 4, 1993. 0 U.S. Cancer Pain Relief Committee, 1993 Published by Elsevier, New York, New York
gia. Reiestad and colleagues!’ and Morrow and Squier”’ suggested that sympathetic inhibition to the upper extremities and head could be accomplished with inter-pleural analgesia. Lema and colleagues” recently reported on the alleviation of chronic pain from metastatic esophageal cancer by inj acting phenol through an interpleural catheter. We describe the use of LPAas the first choice of nerve-block therapy in patients with acute exacerbations of cancer pain thought to be mediated by either thoracic spinal or sympathetic nerve fibers.
Case The investigational review board at Rowe11 Park Cancer Institute approved this study for both retrospective analysis and prospectir;
0885-3924/93/$6.(N)
Vol. 8 No. 7 October 1993
Myers et al.
506
Table 1 Description of Cancer Patients ReceivingInterpleuralAnalgesia Patient no.
Age/ sex
Height (in)/ weight (kg)
Diagnosis-chief
-
pain complaint
51/F
64/72
Metastatic
2
62/F
62/45
Metastatic bronchogenic carcmoma to liver-visceral bilaterally to the upper abdominal quadrants
3
47/M
76/90
Metastatic back
4
45/F
63/60
Metastatic malignant thymoma to heart and chest wall-visceral referred to anterior and lateral chest wall
5
57/F
64/58
Metastatic breast carcinoma to liver-visceral to right upper quadrant and shoulder
6
63/F
66/90
Metastatic breast carcinoma to left axilla-severe neuropathic pain to left arm and shoulder
7
54/M
68/90
somatic pain in left neck, shoulder, Poorly differentiated lymphomaand back from extensive tumor infiltration in skin
8
39/F
70/73
Metastatic breast carcinoma-radiation plexopathy
9
61/F
64/97
Metastatic endometrial carcinoma to thoracic wall-somatic referred pain to right chest and shoulder
10
48/F
63/55
Metastatic breast carcinoma--severe neuropathic pain, reflex sympathetic
1
study. Over a 12-mo period, interpleural catheters were inserted into ten terminally ill patients who were referred to the Roswell Park Cancer Pain Service with intractable pain from a variety of metastatic cancers (Table .I). Four patients had breast cancer and one each had pancreatic cancer, lymphoma, lung ,canccr, renal cancer, malignant thymoma, and endometrial cancer. All patients had diffuse metastascs, primarily in the head, neck, chest, arms, or upper abdominal viscera, and all had severe oain (verbal pain scores of 7/10 or greater) unrelieved by continuous intravenous opioid infusions with patient-controlled analgesia. Every patient who consented to have an interpleural catheter inserted was also eligible to receive one of the following procedures: celiac plexus block, thoracic epidural block, stellate ganglion block, intercostal nerve block, or brachial plexus block. All patients required immediate relief of intractable pain at the time of examination. Each agreed to undergo interpleural therapy instead of titrating pharmacologic therapy and/or waiting for preparations to be made for attempting the traditional nerve block. An interpleural catheter was inserted within 1 hr after consultation in an attempt to reduce pain
pancreatic
carcinoma-visceral
renal carcinoma
pain referred
to bone-somatic
to the back
pain referred
pain in right chest and
subcapsular
induced
lymphedema dystrophy
pain
pain referred
lymphedema
and
right brachial and
in right arm,
intensity rapidly. If the pain was not quickly relieved to the patient’s satisfaction, more traditional nerve blocks would have been subsequently attempted. All interpleural catheters were inserted in the operating room with the patient under local anesthesia and in sterile conditions. An interpleural anesthesia kit (Arrow International, Reading, PA) using a 17-gauge Tuohy needle, IO-mL glass syringe, and a soft flexib!etipped catheter was used. Patients were positioned according to where we wished the bulk of the local anesthetic solution to flow in order to bathe those nerves thought to be responsible for the pain. Interpleural catheter insertion was performed using a passive loss of resistance technique as described by Reiestad and Stromskag.tz Bupivacaine was injected with the affected side upward in all but one patient. The block was administered to patient 2 in the sitting position to alleviate right upper abdominal quadrant pain from hepatic tumor subcapsular distention. Bolus injections of bupivacaine, O-375%, 0.5%, or 0.5% plus 1:200,000 epinephrine were administered in 5-mL increments until verbal pain scores of 3 or less were elicited. Six of ten patients received 0.375%
IJ_d.8 No. 7 October 1993
Inte$euml
Analgesia for &m-e Cuncer Pain
interpleural bupivacaine infusions at our discretion. Rationale for the use of continuous infusions was based on the severity and nature of pain, and the anticipated duration of the patient’s suI%val. Bolus injections were administered to the remainder of the patients to determine the effectiveness and duration of analgesia. AI1 patients remained in the hospital while their catheters were in place and were visited two or three times daily by the pain team to assess their response to the injections or infusions, and their satisfaction with the results of treatment. All patients who received interpleural bupivaCaine experienced complete or nearcomplete cessation of severe pain within 15 min iTable 2). The average b&us itijection of bupivacaine used to reduce the pain was 116 mg (range, 56-I 75 mg). Duration of pain relief by bolus injection ranged from 7 hr to 21 days. As seen in Table 3, six of ten patients experienced minimal pain requiring no further therapy after either intermittent bolus injection or continuous infusion. To date, nine patients have died, all of whom had minimal (<3/10) or no pain at the time of death. No side effects were reported by the patients, nursing staff, or pain team members evaluating them. Two patients who were successfully treated with IPA requested nerve blocks while in minimal pain to achieve complete pain relief. In patient 10, pain gradually intensified to a verbal pain score of 7/ 10 a week after an interpleural bolus injection. She experienced severe dysesthetic, neuropathic pain due to a combination of both tumor recurrence, and radiation fibrosis affecting the brachial plexus. A shoulder disarticulation was performed for both therapeutic and palliative reasons.
The care of terminally ill cancer patients with severe pain is a challenging endeavor. Patients are beyond curative therapy, and pain control together with restoration of an active level of functioning are the primary goals. Several studies have shown that up to 90% of all patients with moderate to severe pain can effectively be treated by oral or parenteral medications.1s.‘4 Patients who are not able to achieve adequate pain relief with pharmacotherapy alone are candidates for other interventions, including neuml blockade.
SO7
In this series of patients, an interpleural analgesic technique performed well when attempting to (a) rapidly reduce acute exacerbations of cancer pain, (b) sustain a relatively pain-free state by bolus injection or short-term continuous infusion, and (c) provide satisfactory analgesia via continuous infusion for moribund patients in pain until their death. Trzditionai nel4 blockade techniques can be very effective in reducing pain in terminally ill patients as well. However, when these techniques fail because of inability to deliver sufficient drug due to tumor spread or altered anatomy, interpleural analgesia may be an effective route. We used as a rapid technique to alleviate pain within an hour of receiving the consultation. Even under conditions of performing the procedure in the operating room, all initial blocks prodttced satisfactory analgesia within that time inteIva1. Interpleural analgesia can also be performed in a procedure room on the nursing unit if the appropriate monitoring devices and resuscitation equipment are available. The onset of analgesia generally occurs within 10 min and persists for at least 7 hr after a single bolus injection. The use of continuous local anesthetic infusions prolongs analgesia until more definitive or neurolydc techniques can be performed. More importantly, the block itself is capable of terminating the presence of a pain cycle condition either by repeated bolus injections or continuous infusions of local anesthetic. The specific regimen was selected based on the patient’s anticipated life expectancy, or in an effort to provide lasting pain relief by interrupting a cycle of neuropathic pain as is recommended for treatment of reflex sympathetic dystrophy (RSD) .4.!‘,10 Interpleural analgesia also may be a useful diagnostic tool for predicting the eff%zac-y of permanent neurolytic blocks. Our clinic recently treated a patient who ultimately received a neurolytic phenol interpleural block after two successful but short-lived interpleural bupivaCaine injections were attempted.” Clinical trials predicting the success of neurolytic interpleural blocks after bupivacaine IPA need to be conducted. The two most obvious potential complications of IPA-clinically significant pneumothorax and local anesthetic toxicity-were not detected in any patient. However, if pneumothorax were detected, the catheter may well
62/F
57/F
47/M
45/F
63/F
54/M
39/F
61/F
48/F
2
3
4
5
6
7
8
9
10
Breast cancer (brachial plexopathy)
Endometrial cancer (chest wall metastasis)
Breast cancer (brachial plexopathy)
Lymphoma (neck, shoulder involvement)
Breast cancer (brachial plexopathy)
Malignant thymoma (heart, pleural involvement)
Renal cancer (bone metastases)
Breast cancer (liver metastases)
Lung cancer (liver metastases)
Pancreaticcancer
Diagnosis
ill rcquiriug palliative arc. Uupivacainc includes 1:200.000 cpiurphrinc. “Win scow indicawd w.wmcs that 0 = 110 pain and 10 = worst im&tablc “Morphinc added to inl’usioll al a raw 0!‘0.5 @hr.
All paticuLs wcrc tcrrnirlally
51/F
1
Age/sex
(30) (30)
(:S5::
(35)
(30)
(30)
(20) (20) (30) (30)
(20) (20)
(20) (20)
;: 75
pain. Wc judged
(20) (20) (20)
56.25 (15)
150 150
175
175
112.5
150
100 100 150 150
100 100
100 136
Bolus mg (cc)
Bupivacaine
O-3 as
z
-
u~iniu~al pain.
6.0 -
-
18.75 -
18.75 -
15.0 -
18.75O -
-
7.0
-
piu,
2.0 2.0 7.0
8.0
until pain.
relief.
Minimal pain achieved after third block, gradually returned to 7/10; had disarticulation.
Moderate pain; requested intercostal phenol block; died in minimal pain 30 days later.
Mild pain; requested stellate block, excellent
Infusion continued until death-pain ft ee.
Infusion continued death-minimal
Relapse (7/l(1) controlled with oral morphine until death; died in minimal pain.
Infusion tapered over 10 days; died in minimal pain.
Died in minimal pain.
Moderate pain” recurred; requested celiac plexus block; died in minimal pain after 1 mo.
Died pain free.
Comment
aild 7-11: as SWCTCpill.
1.0 7.0
7.0
17.0
21.0
40.0
1.0 1.0 5.0 10.0
0.5 0.25 2.0
2.0 21.0
Duration of analgesia (days)
4-6 as uwdcratc
5-O 5+2 2-10
8-10
lO+O 5+0
7-10
7+0
lO+O
IO+0
741 5+0 7-10 7-10
7+0 7+1 740
7+0 7-+0
.-
Change in pain score
Infusion mg/hr
dose
Table2 Efficacy of Interpleural Anesthesia in Advanced Cancer Pain Management
Vol. 8 No. 7 October I993
Interpleural Analgesia for Severe Cancer Pain
509
Table 3 Dwation of Effective
gesia by Using Interpleural Bslus IInjections No. of patient injections
Duration (days) 0.25-l l-3 4-10 1 l-20 21-40
6 (60) 9 (90) 4 (40)
Sustained
1 (10)
thoracic
tunneled intrapleural catheters in the long-term relief of right upper quadrant pain of malignant 0rigin.J Pain Symptom Manage 19389;4:8%39.
severe pain after ail therapy
been
used
ous
3. Reiestad
No. of patienu (%)
Sustainedminimalor no pain Minimalor no pain at death Required nenre block or surgery
have
2. Waldman SD, Allen ML, Cronen MC. Subcutane-
5 4 6 1 3
Results of therapy
to evacuate
air
from
1. Durrani A, Winnie AP, Ikuta P. Interpieural catheter analgesia for pancreatic pain. Anesth Anaig 1988;67:479-481.
F. Kvalheim L, McIivaine WB. Pleural analgesia for the treatment of acutp severe thoracic herpes zoster. Reg Anesth 1989;14:244-246. 4. Ahlburg P, Noreng M, Molgaard J, Egebo K. Treatment of pancreatic pain with interpleural bupivacaine: an open trial. Acta Anaesthesiol Stand 1990;34:15&157. 5. Fineman SP. Long-term post-thoracotomy cancer pain management with interpleural bupivacaine. Anesth Anaig 1989;68:694-697.
the
cavity.
To avoid toxicity, single doses of bupivacaine
should not exceed 225-250 mg.” Single doses limited to 150 mg and infusions of less than 20 mg/hr were administered without toxicity. Because the half-life of bupivacaine is approximately 3.5 hr, the risk of toxicity was low. Tachyphylaxis of local anesthetics delivered by bolus injection or continuous inftlsian has been previously reported to occur as lipid depots become satmated with local ant+ thetic.“‘J7 However, no tachyphylaxis was detected even after 1 wk of bupivacairrc ir;filsion. Since the first use of II?A by Reiestad and Stromskag for postoperative analgesia, many investigators have employed it for a variety of procedures. It has been successfully used as the sole anesthetic technique for biopsies and percutaneous procedures,‘RTPg postoperative analgesia,122021 and chronic pain thempy.‘“~’ ’ Based on our report of these ten cases, we believe that IPA is also effective in rapidly attenuating acute exacerbations of’ cancer pain, providing short-term analgesia for dying pain patients, and terminating a neur,opathic pain cycle similar to those experienced by R!3D patients. However, clinical trials comparing the onset, quality and duration of analgesia produced by IPA with traditional neural blocks should be conducted before conclusive statements regarding IF’A’s clinical benefit can be made.
6. Johnson LR, Rocco AC, Ferrante FM. Continuous subpleural-paravertebral block in acute thoracic herpes roster. Anesth Anaig 1988;67:! 105-l 198. 7. Sihota MK, Holmblad BR. Horner’s syndrome after interpleural anesthesia with bupivacaine for post-herpetic neuralgia. Acta Anaesth Stand 1988; 32:593-594. 8. Reiestad F, Mclhaine WB, Barnes MD, Kvalheim L, Haraidstad P, Pettersen B. Interpleural analgesia in the treatment of severe thoracic postherpetic ueuralgia. Keg Anesth 1990;15:113-117. 9. Reiestad F, McIlvaine WB, Kvalheim L, Stokkc T, Pettersen B. Interpleural analgesia in treatment of extremity reflex sympathetic dystrophy. upper Anesth Anaig 19&9;69:671-673. 10. Morrow JS, Squier RC. Sympathetic blockade wivith interpleural analgesia. Anesthesiology 1989; 71:A662. 11. LPma MJ, Myers DP, de Lieon-Casasola OA, Penetrante R. Pleural phenol therapy for the treatment oFchronic esophageal cancer pain. Reg Anesth 1992;17:166-170. 12. Reiestad F, Stromskag KE. Interpleural catheter in the management of postoperative pain: a preiiminary report. Reg Anesth 1986;11:89-91. 13. Takeda F. Results of field-testing in Japan of the WHO draft interim guideline on relief of cancer pain. Pain Ciin 1986;1:83-89. 14. Walsh TD, Saunders GM. Oral morphine for of cancer pain. N Engi J Med l981;305:14171418.
relief
15. Covino BG. Clinical pharmacology of local anesthetic agents [Table]. In: Cousins MJ, Bridenbaugh PO, eds. Neural blockade in clinical anesthesia and management of pain, 2nd ed. Philadelphia: JB Lippincott, 1988:112. 16. Bromage
PR, Pettivew RT, Crow11 DE. Tachyanesthesia. I. Augmentation and
phylais in epidural
Myers et al.
510
decay of local 1969;9:30-39.
anesthesia.
J
Clin
Pharmacol
17. Tucker CT, Mather LT. Clinical pharmacokinetits of local anesthetic agents. Clin Pharmacokinet 1979;4:241-278. 18. Schlesinger TM, Laurito CE, Baughman VL, Carranza CJ. Interpleural bupivacaine for mammography during needle localization and breast biopsy. Anesth Analg 1989;68:394-395. 19. Narenda
ST, Robalino
J* Shevda
K_ Intrapleural
Vol. 8 No. 7 October .- 1993
block: a new technique for regional anestflesia during percutaneous nephrotomy and nephrolithotomy. Reg Anesth 1989;14:48. 20. McIlvaine WB, Knox, RF, Fennessey PV, Goldstein M. Coutinuous X&on of bupivacaine via intrapleural catheter for anesthesia after thoracotomy in children. Anesthesiology 1988;69:161-264. 21. Laurito CE, Kinz LI, VadeBoncouer TR, et al. Continuous infusion of intrapleural bupivacaine maintains effective analgesia after cholecystectomy. Anesth Analg 1991;72:516-521.
Journal ofPain and Symptom Management
505
David P. Myers, MD, MarkJ. Lema, MD, Oscar A. de Leon-Casasola, MD, and Douglas R. Bacon, MD Bejwtmtwt ofAnesthesioloa und Critical Care Medicine, Roswell Park Cancer Institute, and State University of New Yortiat BuflaLo School of Medicine, Buffalo, New Ymk
Interpleural analpia was used to alleviate acute, severe exacerbations of chronic pain unrelieved bq’pharmacologic therapy in ten terminal& ill cancerpatients. Pain from mPta.static disease to the neck, arms, chest, brachial plexus, thorax, or abdomen was effectivel_yeliminated between 7 hr and 40 o@s in nine patients, who died with minimal or no pain. The technique was pe@med fiSrna+ using bupivacaine. No side effects were detected. Interpleural analgesia appears to be effective in rapidly controlling acute exacerbations of cancer pain in terminally ill patients. Mcrreover, it may also be a suitable thapy for moribund patients when used as a continuous-infK$ion tpchnique. J Pain Symptom Manage 1993;8:505-510.
Chronic pain, cancer
pain, terminally ill, in&$&Ural analgesia
Recent reports have suggested that interpleural analgesia (IPA) may be of long-term benefit to patients suffering from extrapleural pain Fyndromes. 1-4 Durrani and colleagues’ and Ahlburg and colleagues4 alleviated severe pancreatic pain with interpleural bupivacaine, and Fineman found it useful in treating postthoracotomy pain syndromes. Johnson and colleagues,” Sihota and Holmblad,7 and Reiestad and colleaguesX used this technique to treat acute herpes zoster and postherpetic neural-
Address ybrint requests to: Mark J.
Lema, MD, Department of Anesthesiology and Pain Medicine, Roswll Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 142630001, USA. Acceptedfor publication: May 4, 1993. 0 U.S. Cancer Pain Relief Committee, 1993 Published by Elsevier, New York, New York
gia. Reiestad and colleagues!’ and Morrow and Squier”’ suggested that sympathetic inhibition to the upper extremities and head could be accomplished with inter-pleural analgesia. Lema and colleagues” recently reported on the alleviation of chronic pain from metastatic esophageal cancer by inj acting phenol through an interpleural catheter. We describe the use of LPAas the first choice of nerve-block therapy in patients with acute exacerbations of cancer pain thought to be mediated by either thoracic spinal or sympathetic nerve fibers.
Case The investigational review board at Rowe11 Park Cancer Institute approved this study for both retrospective analysis and prospectir;
0885-3924/93/$6.(N)
Vol. 8 No. 7 October 1993
Myers et al.
506
Table 1 Description of Cancer Patients ReceivingInterpleuralAnalgesia Patient no.
Age/ sex
Height (in)/ weight (kg)
Diagnosis-chief
-
pain complaint
51/F
64/72
Metastatic
2
62/F
62/45
Metastatic bronchogenic carcmoma to liver-visceral bilaterally to the upper abdominal quadrants
3
47/M
76/90
Metastatic back
4
45/F
63/60
Metastatic malignant thymoma to heart and chest wall-visceral referred to anterior and lateral chest wall
5
57/F
64/58
Metastatic breast carcinoma to liver-visceral to right upper quadrant and shoulder
6
63/F
66/90
Metastatic breast carcinoma to left axilla-severe neuropathic pain to left arm and shoulder
7
54/M
68/90
somatic pain in left neck, shoulder, Poorly differentiated lymphomaand back from extensive tumor infiltration in skin
8
39/F
70/73
Metastatic breast carcinoma-radiation plexopathy
9
61/F
64/97
Metastatic endometrial carcinoma to thoracic wall-somatic referred pain to right chest and shoulder
10
48/F
63/55
Metastatic breast carcinoma--severe neuropathic pain, reflex sympathetic
1
study. Over a 12-mo period, interpleural catheters were inserted into ten terminally ill patients who were referred to the Roswell Park Cancer Pain Service with intractable pain from a variety of metastatic cancers (Table .I). Four patients had breast cancer and one each had pancreatic cancer, lymphoma, lung ,canccr, renal cancer, malignant thymoma, and endometrial cancer. All patients had diffuse metastascs, primarily in the head, neck, chest, arms, or upper abdominal viscera, and all had severe oain (verbal pain scores of 7/10 or greater) unrelieved by continuous intravenous opioid infusions with patient-controlled analgesia. Every patient who consented to have an interpleural catheter inserted was also eligible to receive one of the following procedures: celiac plexus block, thoracic epidural block, stellate ganglion block, intercostal nerve block, or brachial plexus block. All patients required immediate relief of intractable pain at the time of examination. Each agreed to undergo interpleural therapy instead of titrating pharmacologic therapy and/or waiting for preparations to be made for attempting the traditional nerve block. An interpleural catheter was inserted within 1 hr after consultation in an attempt to reduce pain
pancreatic
carcinoma-visceral
renal carcinoma
pain referred
to bone-somatic
to the back
pain referred
pain in right chest and
subcapsular
induced
lymphedema dystrophy
pain
pain referred
lymphedema
and
right brachial and
in right arm,
intensity rapidly. If the pain was not quickly relieved to the patient’s satisfaction, more traditional nerve blocks would have been subsequently attempted. All interpleural catheters were inserted in the operating room with the patient under local anesthesia and in sterile conditions. An interpleural anesthesia kit (Arrow International, Reading, PA) using a 17-gauge Tuohy needle, IO-mL glass syringe, and a soft flexib!etipped catheter was used. Patients were positioned according to where we wished the bulk of the local anesthetic solution to flow in order to bathe those nerves thought to be responsible for the pain. Interpleural catheter insertion was performed using a passive loss of resistance technique as described by Reiestad and Stromskag.tz Bupivacaine was injected with the affected side upward in all but one patient. The block was administered to patient 2 in the sitting position to alleviate right upper abdominal quadrant pain from hepatic tumor subcapsular distention. Bolus injections of bupivacaine, O-375%, 0.5%, or 0.5% plus 1:200,000 epinephrine were administered in 5-mL increments until verbal pain scores of 3 or less were elicited. Six of ten patients received 0.375%
IJ_d.8 No. 7 October 1993
Inte$euml
Analgesia for &m-e Cuncer Pain
interpleural bupivacaine infusions at our discretion. Rationale for the use of continuous infusions was based on the severity and nature of pain, and the anticipated duration of the patient’s suI%val. Bolus injections were administered to the remainder of the patients to determine the effectiveness and duration of analgesia. AI1 patients remained in the hospital while their catheters were in place and were visited two or three times daily by the pain team to assess their response to the injections or infusions, and their satisfaction with the results of treatment. All patients who received interpleural bupivaCaine experienced complete or nearcomplete cessation of severe pain within 15 min iTable 2). The average b&us itijection of bupivacaine used to reduce the pain was 116 mg (range, 56-I 75 mg). Duration of pain relief by bolus injection ranged from 7 hr to 21 days. As seen in Table 3, six of ten patients experienced minimal pain requiring no further therapy after either intermittent bolus injection or continuous infusion. To date, nine patients have died, all of whom had minimal (<3/10) or no pain at the time of death. No side effects were reported by the patients, nursing staff, or pain team members evaluating them. Two patients who were successfully treated with IPA requested nerve blocks while in minimal pain to achieve complete pain relief. In patient 10, pain gradually intensified to a verbal pain score of 7/ 10 a week after an interpleural bolus injection. She experienced severe dysesthetic, neuropathic pain due to a combination of both tumor recurrence, and radiation fibrosis affecting the brachial plexus. A shoulder disarticulation was performed for both therapeutic and palliative reasons.
The care of terminally ill cancer patients with severe pain is a challenging endeavor. Patients are beyond curative therapy, and pain control together with restoration of an active level of functioning are the primary goals. Several studies have shown that up to 90% of all patients with moderate to severe pain can effectively be treated by oral or parenteral medications.1s.‘4 Patients who are not able to achieve adequate pain relief with pharmacotherapy alone are candidates for other interventions, including neuml blockade.
SO7
In this series of patients, an interpleural analgesic technique performed well when attempting to (a) rapidly reduce acute exacerbations of cancer pain, (b) sustain a relatively pain-free state by bolus injection or short-term continuous infusion, and (c) provide satisfactory analgesia via continuous infusion for moribund patients in pain until their death. Trzditionai nel4 blockade techniques can be very effective in reducing pain in terminally ill patients as well. However, when these techniques fail because of inability to deliver sufficient drug due to tumor spread or altered anatomy, interpleural analgesia may be an effective route. We used as a rapid technique to alleviate pain within an hour of receiving the consultation. Even under conditions of performing the procedure in the operating room, all initial blocks prodttced satisfactory analgesia within that time inteIva1. Interpleural analgesia can also be performed in a procedure room on the nursing unit if the appropriate monitoring devices and resuscitation equipment are available. The onset of analgesia generally occurs within 10 min and persists for at least 7 hr after a single bolus injection. The use of continuous local anesthetic infusions prolongs analgesia until more definitive or neurolydc techniques can be performed. More importantly, the block itself is capable of terminating the presence of a pain cycle condition either by repeated bolus injections or continuous infusions of local anesthetic. The specific regimen was selected based on the patient’s anticipated life expectancy, or in an effort to provide lasting pain relief by interrupting a cycle of neuropathic pain as is recommended for treatment of reflex sympathetic dystrophy (RSD) .4.!‘,10 Interpleural analgesia also may be a useful diagnostic tool for predicting the eff%zac-y of permanent neurolytic blocks. Our clinic recently treated a patient who ultimately received a neurolytic phenol interpleural block after two successful but short-lived interpleural bupivaCaine injections were attempted.” Clinical trials predicting the success of neurolytic interpleural blocks after bupivacaine IPA need to be conducted. The two most obvious potential complications of IPA-clinically significant pneumothorax and local anesthetic toxicity-were not detected in any patient. However, if pneumothorax were detected, the catheter may well
62/F
57/F
47/M
45/F
63/F
54/M
39/F
61/F
48/F
2
3
4
5
6
7
8
9
10
Breast cancer (brachial plexopathy)
Endometrial cancer (chest wall metastasis)
Breast cancer (brachial plexopathy)
Lymphoma (neck, shoulder involvement)
Breast cancer (brachial plexopathy)
Malignant thymoma (heart, pleural involvement)
Renal cancer (bone metastases)
Breast cancer (liver metastases)
Lung cancer (liver metastases)
Pancreaticcancer
Diagnosis
ill rcquiriug palliative arc. Uupivacainc includes 1:200.000 cpiurphrinc. “Win scow indicawd w.wmcs that 0 = 110 pain and 10 = worst im&tablc “Morphinc added to inl’usioll al a raw 0!‘0.5 @hr.
All paticuLs wcrc tcrrnirlally
51/F
1
Age/sex
(30) (30)
(:S5::
(35)
(30)
(30)
(20) (20) (30) (30)
(20) (20)
(20) (20)
;: 75
pain. Wc judged
(20) (20) (20)
56.25 (15)
150 150
175
175
112.5
150
100 100 150 150
100 100
100 136
Bolus mg (cc)
Bupivacaine
O-3 as
z
-
u~iniu~al pain.
6.0 -
-
18.75 -
18.75 -
15.0 -
18.75O -
-
7.0
-
piu,
2.0 2.0 7.0
8.0
until pain.
relief.
Minimal pain achieved after third block, gradually returned to 7/10; had disarticulation.
Moderate pain; requested intercostal phenol block; died in minimal pain 30 days later.
Mild pain; requested stellate block, excellent
Infusion continued until death-pain ft ee.
Infusion continued death-minimal
Relapse (7/l(1) controlled with oral morphine until death; died in minimal pain.
Infusion tapered over 10 days; died in minimal pain.
Died in minimal pain.
Moderate pain” recurred; requested celiac plexus block; died in minimal pain after 1 mo.
Died pain free.
Comment
aild 7-11: as SWCTCpill.
1.0 7.0
7.0
17.0
21.0
40.0
1.0 1.0 5.0 10.0
0.5 0.25 2.0
2.0 21.0
Duration of analgesia (days)
4-6 as uwdcratc
5-O 5+2 2-10
8-10
lO+O 5+0
7-10
7+0
lO+O
IO+0
741 5+0 7-10 7-10
7+0 7+1 740
7+0 7-+0
.-
Change in pain score
Infusion mg/hr
dose
Table2 Efficacy of Interpleural Anesthesia in Advanced Cancer Pain Management
Vol. 8 No. 7 October I993
Interpleural Analgesia for Severe Cancer Pain
509
Table 3 Dwation of Effective
gesia by Using Interpleural Bslus IInjections No. of patient injections
Duration (days) 0.25-l l-3 4-10 1 l-20 21-40
6 (60) 9 (90) 4 (40)
Sustained
1 (10)
thoracic
tunneled intrapleural catheters in the long-term relief of right upper quadrant pain of malignant 0rigin.J Pain Symptom Manage 19389;4:8%39.
severe pain after ail therapy
been
used
ous
3. Reiestad
No. of patienu (%)
Sustainedminimalor no pain Minimalor no pain at death Required nenre block or surgery
have
2. Waldman SD, Allen ML, Cronen MC. Subcutane-
5 4 6 1 3
Results of therapy
to evacuate
air
from
1. Durrani A, Winnie AP, Ikuta P. Interpieural catheter analgesia for pancreatic pain. Anesth Anaig 1988;67:479-481.
F. Kvalheim L, McIivaine WB. Pleural analgesia for the treatment of acutp severe thoracic herpes zoster. Reg Anesth 1989;14:244-246. 4. Ahlburg P, Noreng M, Molgaard J, Egebo K. Treatment of pancreatic pain with interpleural bupivacaine: an open trial. Acta Anaesthesiol Stand 1990;34:15&157. 5. Fineman SP. Long-term post-thoracotomy cancer pain management with interpleural bupivacaine. Anesth Anaig 1989;68:694-697.
the
cavity.
To avoid toxicity, single doses of bupivacaine
should not exceed 225-250 mg.” Single doses limited to 150 mg and infusions of less than 20 mg/hr were administered without toxicity. Because the half-life of bupivacaine is approximately 3.5 hr, the risk of toxicity was low. Tachyphylaxis of local anesthetics delivered by bolus injection or continuous inftlsian has been previously reported to occur as lipid depots become satmated with local ant+ thetic.“‘J7 However, no tachyphylaxis was detected even after 1 wk of bupivacairrc ir;filsion. Since the first use of II?A by Reiestad and Stromskag for postoperative analgesia, many investigators have employed it for a variety of procedures. It has been successfully used as the sole anesthetic technique for biopsies and percutaneous procedures,‘RTPg postoperative analgesia,122021 and chronic pain thempy.‘“~’ ’ Based on our report of these ten cases, we believe that IPA is also effective in rapidly attenuating acute exacerbations of’ cancer pain, providing short-term analgesia for dying pain patients, and terminating a neur,opathic pain cycle similar to those experienced by R!3D patients. However, clinical trials comparing the onset, quality and duration of analgesia produced by IPA with traditional neural blocks should be conducted before conclusive statements regarding IF’A’s clinical benefit can be made.
6. Johnson LR, Rocco AC, Ferrante FM. Continuous subpleural-paravertebral block in acute thoracic herpes roster. Anesth Anaig 1988;67:! 105-l 198. 7. Sihota MK, Holmblad BR. Horner’s syndrome after interpleural anesthesia with bupivacaine for post-herpetic neuralgia. Acta Anaesth Stand 1988; 32:593-594. 8. Reiestad F, Mclhaine WB, Barnes MD, Kvalheim L, Haraidstad P, Pettersen B. Interpleural analgesia in the treatment of severe thoracic postherpetic ueuralgia. Keg Anesth 1990;15:113-117. 9. Reiestad F, McIlvaine WB, Kvalheim L, Stokkc T, Pettersen B. Interpleural analgesia in treatment of extremity reflex sympathetic dystrophy. upper Anesth Anaig 19&9;69:671-673. 10. Morrow JS, Squier RC. Sympathetic blockade wivith interpleural analgesia. Anesthesiology 1989; 71:A662. 11. LPma MJ, Myers DP, de Lieon-Casasola OA, Penetrante R. Pleural phenol therapy for the treatment oFchronic esophageal cancer pain. Reg Anesth 1992;17:166-170. 12. Reiestad F, Stromskag KE. Interpleural catheter in the management of postoperative pain: a preiiminary report. Reg Anesth 1986;11:89-91. 13. Takeda F. Results of field-testing in Japan of the WHO draft interim guideline on relief of cancer pain. Pain Ciin 1986;1:83-89. 14. Walsh TD, Saunders GM. Oral morphine for of cancer pain. N Engi J Med l981;305:14171418.
relief
15. Covino BG. Clinical pharmacology of local anesthetic agents [Table]. In: Cousins MJ, Bridenbaugh PO, eds. Neural blockade in clinical anesthesia and management of pain, 2nd ed. Philadelphia: JB Lippincott, 1988:112. 16. Bromage
PR, Pettivew RT, Crow11 DE. Tachyanesthesia. I. Augmentation and
phylais in epidural
Myers et al.
510
decay of local 1969;9:30-39.
anesthesia.
J
Clin
Pharmacol
17. Tucker CT, Mather LT. Clinical pharmacokinetits of local anesthetic agents. Clin Pharmacokinet 1979;4:241-278. 18. Schlesinger TM, Laurito CE, Baughman VL, Carranza CJ. Interpleural bupivacaine for mammography during needle localization and breast biopsy. Anesth Analg 1989;68:394-395. 19. Narenda
ST, Robalino
J* Shevda
K_ Intrapleural
Vol. 8 No. 7 October .- 1993
block: a new technique for regional anestflesia during percutaneous nephrotomy and nephrolithotomy. Reg Anesth 1989;14:48. 20. McIlvaine WB, Knox, RF, Fennessey PV, Goldstein M. Coutinuous X&on of bupivacaine via intrapleural catheter for anesthesia after thoracotomy in children. Anesthesiology 1988;69:161-264. 21. Laurito CE, Kinz LI, VadeBoncouer TR, et al. Continuous infusion of intrapleural bupivacaine maintains effective analgesia after cholecystectomy. Anesth Analg 1991;72:516-521.