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Continuous epidural morphine treatment for intractable pain in terminal cancer patients
311
Pain, 14 (1982) 311-315 Elsevier Biomedical Press
Clinical Note
Continuous Epidural Morphine Treatment for Intractable Pain in Terminal Cancer Patients Gideon
Findler
‘, David Olshwang
* and Moshe Hadani
Department
of Neurosurgery and * Anaesthesiology, Hadassah University Medical Center, Ein - Kerem, Jerusalem (Israel) (Received
30 December
1981, accepted
26 March
1982)
Summary In patients with intractable cancer pain who failed to respond to conservative and neurosurgical procedures for pain relief, repeated injections of epidural morphine were found to be beneficial. A small dose of morphine (2-4 mg per injection) relieved pain for 6-24 h. A permanent subcutaneous epidural catheter led to successful ambulatory treatment without complications. The implantation of the epidural catheter is a minor surgical procedure, done under local anesthesia and is considered safe even in terminal cancer patients.
Introduction Intractable pain most often plays a major role in debilitated patients with advanced cancer, especially with local invasion and metastases. Such pain often does not respond to oral or parenteral narcotics commonly used in these patients [ 1,5]. Other methods, such as local irradiation of the painful sites as well as a variety of neurosurgical procedures often fail to abolish the pain, have a relatively high complication rate and their use is limited due to the poor general condition of these patients [3]. Moreover, even after successful cordotomy or commissurotomy, pain may recur [3]. Pain in patients with advanced cancer of the abdomen and pelvis is often more difficult to control due to the variety of tracts which transmit the pain [3]. Continuous epidural morphine treatment through a permanent subcutaneous catheter has been found to be beneficial in these patients.
’ Correspondence Medical Center,
and reprint requests: Tel Aviv, Israel.
0304-3959/S2/0000-OOOOooo/%O2.75
Dr. G. Findler,
Department
0 1982 Elsevier Biomedical
Press
of Neurosurgery,
Tel-Hashomer
312
Patients and Method Table I gives the details of the patients. All suffered from intractable pain due to inoperable cancer of abdominal or pelvic viscera proven by surgical exploration. Conservative means, such as local irradiation, orally taken narcotics, and transcutaneous stimulation failed to abolish their pain. The patients required frequent high doses of Percodan and Talwin during daytime and sleeping drugs for the night (see Table I). All of these patients were severely debilitated by low back. abdominal or perineal pain, often radiating to the lower limbs.
TABLE
I
DETAILS OF THE CANCER MORPHINE TREATMENT
PATIENTS
WITH
INTRACTABLE
PAIN,
PRIOR
TO EPIDURAL
Age (years) and sex
Site of primary cancer
Site of metastases
Site of pain
Failed treatments
51 M
Colon
Liver Lumbar
Low abdomen Low back Lower limbs
Local irradiation Transcutaneous stimulation Percodan q4h, sleeping pills Valium
Pelvis Lower limbs
Local irradiation Percodan q2-4h followed by Talwin q2h, sleeping pills
Low abdomen Groin
Local irradiation Percodan q2-4h Sleeping pills Valium
Low back Lower limbs
Local irradiation Percodan q2-4h Talwin q2-4h Sleeping pills Valium
Low back Perineum Lower limbs
Local irradiation Percodan q2h Sleeping pills Valium
Low back Lower limbs
Local irradiation Percodan q2h followed Talwin q2h Sleeping pills Valium
41 M
Bladder
68 M
Bladder
58 M
Lung
83 M
67 M
Rectum
Colon
spine
Prostate Lymph nodes Lungs
Spine Hip
Liver Lymph Spine
nodes
Spine
Percodan: oxycodone HCl (100%) 4.5 mg; oxycodone Pharmac. Ltd., Haifa, Israel). Talwin: pentazocine HCl, 50 mg (Winthorp Products
terephthalate Inc.).
(100%) 0.38 mg; aspirin
followed
by
by
325 mg (Taro
313
None were considered fit for any neurosurgical procedure due to poor lung and liver functions. Single repeated injections of morphine, 2-4 mg, diluted in 6-8 ml of normal saline injected into the epidural space through a temporal external epidural catheter produced complete pain relief in all patients for 6-24 h. Following a week of successful treatment through the external catheter, a permanent subcutaneous epidural catheter was inserted. Under local anesthesia with the patient in the lateral position, a small midline skin incision was made at the level of L,-L, interspace. A polyethylene catheter was inserted in the epidural space appro~mately 4 cm in the cephalad direction through a 14 gauge Touhy needle. The catheter was tunneled subcutaneously towards the flank and abdominal wall, and connected either to a subcutaneously placed Omthrough a small skin incision and maya reservoir * or had its tip exteriorized connected to a rubber covered plastic tip, secured to the skin with a small sterile bandage. Injections of morphine were initiated on the same day and the patients were discharged on the following day with instructions regarding self-injections.
Results All patients reported complete relief of pain within 20 min of epidural injection of small doses of morphine which lasted for 6-24 h. The patients carried on with 2 injections daily for a period of 4-5 months. There were no neurological signs accompanying the injections. No adverse effects or drug addiction have been encountered. There was no infection or skin reaction along the catheter. In 2 patients a leak from the subcutaneous reservoir led to its removal and the proximal end of the catheter was exteriorized. All of the patients regained their daily activities, abandoned oral medication and sleeping pills; their mood improved significantly. Two of the patients died of their cancer 4 and 5 months following the implantation of the catheter. Discussion Pilon and Baker [6] used local anesthetics (mepivacaine, tetracaine and bupivacaine) injections into a subcutaneous Ommaya reservoir which ended in the epidural space in a patient with chronic cancer pain. However, regardless of the agent they used, a single injection provided at best only 2-3 h of partial relief. Their patient ended up with a thoracic cordotomy. The introduction of epidural morphine by Behar et al. [2] led to its successful use in treatment of various pain conditions. Magora et al. [4] used repeated single
* Ommaya CSF reservoir: Heyer-Schulte
Inc.
314
injections into a temporarily inserted epidural catheter in 16 patients with cancer pain. 12 patients reported complete or marked pain relief for at least 4 h following the administration of morphine. In the remaining 4 patients pain was only diminished, but function was partially improved and use of systemic analgesic drugs was considerably reduced. The mode of action of epidural morphine is not yet clear. It may be related to selective activation of intraspinal endorphins which induce analgesia without affecting the motor or sympathetic system [4]. With administration of small epidural doses of 2-4 mg, the good results of morphine are much better when compared to those achieved using much larger doses of extradural pethidine (100 mg) or intrathecal morphine (20 mg), which also carry the risk of systemic effects [4]. The lack of any adverse side effect, drug addiction and, most important, motor and sphincteric impairment made close and continuous supervision unnecessary and rendered administration of the epidural morphine most suitable for home care. The effect of the small doses is prolonged, and neither the dose nor the frequency of injections had to be increased for as long as 4 months. The site of injection in relation to the painful areas is crucial and the drug should be applied at the level innervating the pain focus, The same technique, with the tip of the catheter placed higher up, can probably be used in patients with cancer pain in their thorax and upper extremities. However, caution must be taken as to respiratory and hemodynamic failure [7]. The only complication which has been encountered was leakage at the subcutaneous reservoir. This was further prevented by instructing the patient to change the site of injections as frequently as possible. Improvement of mood in all patients is one of the most important beneficial feature of the epidural morphine treatment in patients suffering from chronic pain due to cancer.
Addendum After this work has been completed a very similar one has been published by Poletti et al. (J. Neurosurg., 55 (1981) 581-584). Interestingly, these authors had the same experience with epidural morphine repeatedly injected in similar small doses.
References 1 Beaver, W.T., Management 2653-2651. 2 Behar, M., Olshwang, D., Lancet, i (1979) 527-529. 3 Black, P., Management of 4 Magora, F., Olshwang, D., in various pain conditions,
of cancer Magora.
pain with parenteral F. and Davidson,
medication,
J.T., Epidural
cancer pain: an overview, Neurosurgery. Eimeral, D., Shorr, J. et ai., Observations Brit. J. Anaesth., 52 (1980) 247-252.
J. Amer. med. Ass.. 244 (1980) morphine
in treatment
5 (1979) 507-518. on extradural rno~~ine
of pain,
analgesia
315
5 Moertel,
C.G., Treatment
of cancer pain with orally administered
medications,
J. Amer. med. Ass., 244
(1980) 2448-2450. 6 Pilon, R.N. and Baker, A.R., Chronic pain control by means of an epidural catheter. Report of case, Cancer, 37 (1976) 903-905. 7 Samu, K., Feret, J., Harari, A. and Viaes, P., Selective spinal analgesia, Lancet, i (1979) 1142.
Pain, 14 (1982) 311-315 Elsevier Biomedical Press
Clinical Note
Continuous Epidural Morphine Treatment for Intractable Pain in Terminal Cancer Patients Gideon
Findler
‘, David Olshwang
* and Moshe Hadani
Department
of Neurosurgery and * Anaesthesiology, Hadassah University Medical Center, Ein - Kerem, Jerusalem (Israel) (Received
30 December
1981, accepted
26 March
1982)
Summary In patients with intractable cancer pain who failed to respond to conservative and neurosurgical procedures for pain relief, repeated injections of epidural morphine were found to be beneficial. A small dose of morphine (2-4 mg per injection) relieved pain for 6-24 h. A permanent subcutaneous epidural catheter led to successful ambulatory treatment without complications. The implantation of the epidural catheter is a minor surgical procedure, done under local anesthesia and is considered safe even in terminal cancer patients.
Introduction Intractable pain most often plays a major role in debilitated patients with advanced cancer, especially with local invasion and metastases. Such pain often does not respond to oral or parenteral narcotics commonly used in these patients [ 1,5]. Other methods, such as local irradiation of the painful sites as well as a variety of neurosurgical procedures often fail to abolish the pain, have a relatively high complication rate and their use is limited due to the poor general condition of these patients [3]. Moreover, even after successful cordotomy or commissurotomy, pain may recur [3]. Pain in patients with advanced cancer of the abdomen and pelvis is often more difficult to control due to the variety of tracts which transmit the pain [3]. Continuous epidural morphine treatment through a permanent subcutaneous catheter has been found to be beneficial in these patients.
’ Correspondence Medical Center,
and reprint requests: Tel Aviv, Israel.
0304-3959/S2/0000-OOOOooo/%O2.75
Dr. G. Findler,
Department
0 1982 Elsevier Biomedical
Press
of Neurosurgery,
Tel-Hashomer
312
Patients and Method Table I gives the details of the patients. All suffered from intractable pain due to inoperable cancer of abdominal or pelvic viscera proven by surgical exploration. Conservative means, such as local irradiation, orally taken narcotics, and transcutaneous stimulation failed to abolish their pain. The patients required frequent high doses of Percodan and Talwin during daytime and sleeping drugs for the night (see Table I). All of these patients were severely debilitated by low back. abdominal or perineal pain, often radiating to the lower limbs.
TABLE
I
DETAILS OF THE CANCER MORPHINE TREATMENT
PATIENTS
WITH
INTRACTABLE
PAIN,
PRIOR
TO EPIDURAL
Age (years) and sex
Site of primary cancer
Site of metastases
Site of pain
Failed treatments
51 M
Colon
Liver Lumbar
Low abdomen Low back Lower limbs
Local irradiation Transcutaneous stimulation Percodan q4h, sleeping pills Valium
Pelvis Lower limbs
Local irradiation Percodan q2-4h followed by Talwin q2h, sleeping pills
Low abdomen Groin
Local irradiation Percodan q2-4h Sleeping pills Valium
Low back Lower limbs
Local irradiation Percodan q2-4h Talwin q2-4h Sleeping pills Valium
Low back Perineum Lower limbs
Local irradiation Percodan q2h Sleeping pills Valium
Low back Lower limbs
Local irradiation Percodan q2h followed Talwin q2h Sleeping pills Valium
41 M
Bladder
68 M
Bladder
58 M
Lung
83 M
67 M
Rectum
Colon
spine
Prostate Lymph nodes Lungs
Spine Hip
Liver Lymph Spine
nodes
Spine
Percodan: oxycodone HCl (100%) 4.5 mg; oxycodone Pharmac. Ltd., Haifa, Israel). Talwin: pentazocine HCl, 50 mg (Winthorp Products
terephthalate Inc.).
(100%) 0.38 mg; aspirin
followed
by
by
325 mg (Taro
313
None were considered fit for any neurosurgical procedure due to poor lung and liver functions. Single repeated injections of morphine, 2-4 mg, diluted in 6-8 ml of normal saline injected into the epidural space through a temporal external epidural catheter produced complete pain relief in all patients for 6-24 h. Following a week of successful treatment through the external catheter, a permanent subcutaneous epidural catheter was inserted. Under local anesthesia with the patient in the lateral position, a small midline skin incision was made at the level of L,-L, interspace. A polyethylene catheter was inserted in the epidural space appro~mately 4 cm in the cephalad direction through a 14 gauge Touhy needle. The catheter was tunneled subcutaneously towards the flank and abdominal wall, and connected either to a subcutaneously placed Omthrough a small skin incision and maya reservoir * or had its tip exteriorized connected to a rubber covered plastic tip, secured to the skin with a small sterile bandage. Injections of morphine were initiated on the same day and the patients were discharged on the following day with instructions regarding self-injections.
Results All patients reported complete relief of pain within 20 min of epidural injection of small doses of morphine which lasted for 6-24 h. The patients carried on with 2 injections daily for a period of 4-5 months. There were no neurological signs accompanying the injections. No adverse effects or drug addiction have been encountered. There was no infection or skin reaction along the catheter. In 2 patients a leak from the subcutaneous reservoir led to its removal and the proximal end of the catheter was exteriorized. All of the patients regained their daily activities, abandoned oral medication and sleeping pills; their mood improved significantly. Two of the patients died of their cancer 4 and 5 months following the implantation of the catheter. Discussion Pilon and Baker [6] used local anesthetics (mepivacaine, tetracaine and bupivacaine) injections into a subcutaneous Ommaya reservoir which ended in the epidural space in a patient with chronic cancer pain. However, regardless of the agent they used, a single injection provided at best only 2-3 h of partial relief. Their patient ended up with a thoracic cordotomy. The introduction of epidural morphine by Behar et al. [2] led to its successful use in treatment of various pain conditions. Magora et al. [4] used repeated single
* Ommaya CSF reservoir: Heyer-Schulte
Inc.
314
injections into a temporarily inserted epidural catheter in 16 patients with cancer pain. 12 patients reported complete or marked pain relief for at least 4 h following the administration of morphine. In the remaining 4 patients pain was only diminished, but function was partially improved and use of systemic analgesic drugs was considerably reduced. The mode of action of epidural morphine is not yet clear. It may be related to selective activation of intraspinal endorphins which induce analgesia without affecting the motor or sympathetic system [4]. With administration of small epidural doses of 2-4 mg, the good results of morphine are much better when compared to those achieved using much larger doses of extradural pethidine (100 mg) or intrathecal morphine (20 mg), which also carry the risk of systemic effects [4]. The lack of any adverse side effect, drug addiction and, most important, motor and sphincteric impairment made close and continuous supervision unnecessary and rendered administration of the epidural morphine most suitable for home care. The effect of the small doses is prolonged, and neither the dose nor the frequency of injections had to be increased for as long as 4 months. The site of injection in relation to the painful areas is crucial and the drug should be applied at the level innervating the pain focus, The same technique, with the tip of the catheter placed higher up, can probably be used in patients with cancer pain in their thorax and upper extremities. However, caution must be taken as to respiratory and hemodynamic failure [7]. The only complication which has been encountered was leakage at the subcutaneous reservoir. This was further prevented by instructing the patient to change the site of injections as frequently as possible. Improvement of mood in all patients is one of the most important beneficial feature of the epidural morphine treatment in patients suffering from chronic pain due to cancer.
Addendum After this work has been completed a very similar one has been published by Poletti et al. (J. Neurosurg., 55 (1981) 581-584). Interestingly, these authors had the same experience with epidural morphine repeatedly injected in similar small doses.
References 1 Beaver, W.T., Management 2653-2651. 2 Behar, M., Olshwang, D., Lancet, i (1979) 527-529. 3 Black, P., Management of 4 Magora, F., Olshwang, D., in various pain conditions,
of cancer Magora.
pain with parenteral F. and Davidson,
medication,
J.T., Epidural
cancer pain: an overview, Neurosurgery. Eimeral, D., Shorr, J. et ai., Observations Brit. J. Anaesth., 52 (1980) 247-252.
J. Amer. med. Ass.. 244 (1980) morphine
in treatment
5 (1979) 507-518. on extradural rno~~ine
of pain,
analgesia
315
5 Moertel,
C.G., Treatment
of cancer pain with orally administered
medications,
J. Amer. med. Ass., 244
(1980) 2448-2450. 6 Pilon, R.N. and Baker, A.R., Chronic pain control by means of an epidural catheter. Report of case, Cancer, 37 (1976) 903-905. 7 Samu, K., Feret, J., Harari, A. and Viaes, P., Selective spinal analgesia, Lancet, i (1979) 1142.