|Year : 2011 | Volume
| Issue : 2 | Page : 162--165
Successful management of a difficult cancer pain patient by appropriate adjuvant and morphine titration
Shiv PS Rana, Arif Ahmed, Vindo Kumar, Prakash K Chaudhary, Deepa Khurana, Seema Mishra
Unit of Anaesthesiology (IRCH), Dr. BRA Institute Rotary Cancer Hospital, AIIMS, New Delhi, India
Shiv PS Rana
Unit of Anaesthesiology (IRCH), Dr. BRA Institute Rotary Cancer Hospital, AIIMS, New Delhi
Morphine has been used for many years to relieve cancer pain. Oral morphine (in either immediate release or modified release form) remains the analgesic of choice for moderate or severe cancer pain. The dose of oral morphine is titrated up to achieve adequate relief from pain with minimal side effects. Antidepressant and anticonvulsant drugs, when used in addition to conventional analgesics, give excellent relief from cancer pain. Most cancer pain responds to pharmacological measures with oral morphine but some pain like neuropathic and bony pain, pain in children and elderly age group, and advanced malignancy pain are very difficult to treat. Here, we report the management of a similar patient of severe cancer pain and the difficulty that we came across during dose titration of oral morphine and adjuvant analgesic.
|How to cite this article:|
Rana SP, Ahmed A, Kumar V, Chaudhary PK, Khurana D, Mishra S. Successful management of a difficult cancer pain patient by appropriate adjuvant and morphine titration.Indian J Palliat Care 2011;17:162-165
|How to cite this URL:|
Rana SP, Ahmed A, Kumar V, Chaudhary PK, Khurana D, Mishra S. Successful management of a difficult cancer pain patient by appropriate adjuvant and morphine titration. Indian J Palliat Care [serial online] 2011 [cited 2019 Jun 16 ];17:162-165
Available from: http://www.jpalliativecare.com/text.asp?2011/17/2/162/84541
For cancer pain, oral opioid analgesic is the mainstay of treatment. ,, When weak opioids like tramadol, codeine fail to achieve satisfactory pain relief, strong opioids should be incorporated in the treatment plan in accordance with World Health Organization (WHO) guidelines for cancer pain relief.  Consequently, morphine administration should be titrated in each individual to a dose sufficient to provide stable pain relief with an acceptable level of side effects.  The European Association of Palliative Care (EAPC) guidelines for management of cancer pain recommend that titration is performed using oral immediate release morphine given 4 hourly.  But continuous intravenous infusion has an advantage in cases of severe pain when rapid titration and immediate pain relief is needed.  Adjuvant drugs (anxiolytics, anticonvulsants, antidepressants, corticosteroids) may modify the perception of pain and remove the concomitants of pain such as fear, anxiety and depression. These drugs can be primary analgesics, but they are usually added in the treatment plan to supplement primary analgesics. The adjuvant analgesic along with opioid has been used to obtain optimum pain relief with acceptable side effects. This case report highlights the selection of appropriate adjuvant making titration of morphine easy with acceptable side effects.
A 71-year-old female presented with pain and swelling in right gluteal region and the lower limb for 7-8 months. Magnetic resonance imaging (MRI) showed destruction of right pelvic bone with a large soft tissue mass involving right hip joint along with partial collapse of L (lumbar) 2-3 vertebral bodies, diffuse disk bulge at L2-3, L3-4, L4-5, L5-S (sacral) 1 levels compressing the thecal sac. After tissue biopsy and histopathologic examination, the gluteal soft tissue mass was diagnosed as spindle cell sarcoma. Computed tomography (CT) scan of thorax was negative for metastases. But surgery was not possible due to the extent of disease. Therefore, external radiotherapy to right gluteal region and right hemipelvis was given with an aim to reduce the tumor bulk and give pain relief. But there was no relief from pain.
The patient was then referred to Pain clinic, with swelling in right gluteal region and pain radiating to the right leg. The intensity of the pain was reported as a 9 on the 10-point visual analog scale (VAS), with the least pain as 8/10. The pain was constant, and described as burning, sharp, and shocking. The inability to achieve pain relief resulted in lack of sleep, poor quality of life, and severe depression. At this point of time, she was taking tab. codeine 30 mg 6 hourly, but pain relief was only 20% lasting for less than 1 hour. So, oral morphine 10 mg 4 hourly was started and titrated to 15 mg 4 hourly along with ibuprofen and paracetamol combination 8 hourly, cap. pregabalin 75 mg at bedtime along with tab dulcolax and tab. ranitidine twice a day. After 3 days, the patient again came back complaining of pain with a VAS of 8/10.
The patient was then admitted to ward and intravenous morphine infusion at 1.0 mg/hour was started to titrate the dose. Oral methylprednisolone 8 mg 12 hourly was added to reduce tissue edema. After 12 hours, VAS was reduced to only 7/10. Therefore, morphine infusion was increased to 1.5 mg/hour for 12 hours, but VAS could be reduced to only 4/10. So, morphine infusion was further increased to 2.0 mg/hour and then titrated up to 3.0 mg/hour to achieve 100% pain relief, but at this dose of morphine, patient became sedated. Morphine infusion was therefore reduced to 2.5 mg/hour for the next 24 hours and pregabalin dose was increased to 300 mg a day. The patient remained conscious and alert with 1/10 VAS. Then, the patient was shifted to oral morphine 30 mg 4 hourly and pregabalin 150 mg twice a day, and a combination of ibuprofen and paracetamol 8 hourly. She remained awake and alert with 100% pain relief and was discharged.
There is no such thing as a standard dose of morphine.  The goal of morphine therapy is a favorable balance between analgesia and side effects. The dose must be titrated against effect for each patient, and the starting dose should be determined by previous analgesic dose. Whenever shifting from weak opioid to strong opioid, one should start with 10 mg dose every 4 hourly. If the patient is suffering from very severe pain, one can directly prescribe a strong analgesic. During dose titration, it is preferable to use immediate release formulation of morphine because the onset is very rapid, has a definitive effect, and the duration of action is 3-4 hours to allow steady state to be achieved as quickly as possible.  We also used immediate release preparation of oral morphine for optimum pain control. The patient should be evaluated during four to five half-lives (i.e., within 24 hours) after the start of treatment and every dose adjustment, and the dose should be adjusted accordingly. This method of dose titration avoids the need to remember predetermined increments and has been shown to be safe and effective.
The correct dose of an opioid is the dose that effectively relieves pain without inducing unacceptable side effect. Dose requirements may vary a lot, but few patients need very high doses. The adjuvant analgesic drugs include many drugs from various classes. All these drugs are available for indications other than analgesia, but they may be analgesic in select circumstances. Adjuvant analgesics such as antidepressant or anticonvulsant drugs, used alone or in conjunction with a conventional analgesic, have an important role in some patients.  There is no standard or set of doses of narcotics in cancer pain. There is a great variation between individuals. One may experience pain even in the early stage of disease; this should be properly evaluated and treated because every patient has a different pain threshold level and different opioid requirement. Our patient sedated after increment of intravenous morphine dose; this may be due to the fact that by the same time steroid was started, the pain sensation due to compression of structures was relieved after taking steroid as steroid helps in relieving compression symptoms by decreasing the tissue edema. This could have resulted in sedation due to increment of morphine dose.
The relative potency of morphine by intravenous and subcutaneous routes is the same. When converting from oral to intravenous morphine, the oral dose should be divided by three.  If a patient develops inadequate analgesia or suffers intolerable adverse effects despite the optimal use of systemic opioids, spinal administration (epidural or intrathecal) should be considered. The use of spinal opioids is highly controversial,  but it is generally thought that this route should be used as a second-line option in managing cancer pain.
Oral route is the standard route for relief from cancer pain. But when a patient is unable to take oral drugs from causes like mucositis, odynophagia associated with carcinoma base of tongue and carcinoma esophagus, and for patients with very severe pain, who are unable to swallow drugs or experience vomiting/regurgitation, intravenous route should be chosen.  Subcutaneous and rectal route of morphine administration may be an option for terminal ill patients, unable to swallow oral medicines. We used intravenous morphine infusion for immediate pain relief and to titrate the dose of morphine in our patient. It seems that the relative potency ratio varies according to the circumstances in which morphine is used. It also varies among individual patients.
A randomized controlled trial by Harris et al. compared intravenous route with oral route for initial dose titration of morphine in 62 patients with end-stage cancer, having severe pain, and found the intravenous method to be safe, effective and superior to the traditional method in providing immediate relief to severe cancer pain.  In a multicenter study,  28 patients with cancer pain and insufficient pain relief with analgesic treatment according to step II of the guidelines of the WHO were given intravenous morphine initially through a Patient-Controlled Analgesia (PCA) pump for the first 24 hours. From the second day, the patients were treated with oral slow-release morphine. They concluded that dose finding with intravenous PCA may be appropriate for a small minority of patients with severe pain.
The systemic availability of morphine by the oral route is poor and this contributes to a sometimes unpredictable onset of action and great inter-individual variability in dose requirements and response. Some types of pain do not always respond well or completely to morphine, notably neuropathic pain. Addition of proper adjuvant analgesics makes a lot of difference in these patients. However, none of the alternatives to morphine has so far demonstrated advantages, which would make it preferable as the first-line oral opioid for cancer pain. In patients with deranged liver and kidney function, dose of oral or parenteral morphine should be carefully titrated to avoid unnecessary effects due to morphine overdose as a result of accumulation of morphine metabolites.
The role of conventional analgesic is limited in neuropathic pain. Certain adjuvant analgesics like gabapentine and pregabalin have been proven to provide definitive role in these types of pain. Providing sustained analgesia is an important aspect of cancer pain management. Medications should be administered on an around-the-clock basis because regular administration of doses maintains a constant level of drug in the body and helps prevent recurrence of pain. Titration is improved by the more frequent administration of smaller doses, but it is important to use additional doses to initially "load" a patient. The titration of opioids should always be accompanied by the monitoring of pain and sedation scores and ventilation.
In patients with tumor progression, the increase of the analgesic medication might be due to the changing in the clinical situation and disease progression. Dose titration with a potent opioid may be considered as safe and efficient in clinical practice. Nevertheless, the high morbidity and the reduced performance status and compliance, in combination with the analgesic medication, may lead to complications, requiring fast intervention from the medical staff. Our patient also behaved in a similar manner and the high morphine requirement might be the result of progressive nature of the disease.
Admission to palliative care units for dose titration with morphine is required for few patients in their old age, advanced malignancy, bony and neuropathic pain. However, a small minority of cancer patients suffers from pain exacerbations so severe that intravenous dose finding with proper selection of adjuvant drug is necessary for assessment of pain syndromes, planning of the analgesic regimen, and adequate pain management.
|1||Wiffen PJ, McQuay HJ. Oral morphine for cancer pain. Cochrane Database Syst Rev 2007;17:CD003868.|
|2||Lussiera D, Huskeyb AG, Portenoy RK. Adjuvant analgesics in cancer pain management. Oncologist 2004;9:571-91. |
|3||Bonica JJ, Ekstrom JL. Systemic opioids for the management of cancer pain: An updated review. In: Bendetti C, Chapman CR, Giron G, editors. Vol. 14. New York, NY: Raven Press; 1990. p. 425-46. |
|4||World health organization. Cancer pain relief. Geneva, Switzerland: WHO; 1986. |
|5||Klepstad P, Kaasa S, Jystad A, Hval B, Borchgrevink PC. Borchgrevink. Immediate- or sustained-release morphine for dose finding during start of morphine to cancer patients: a randomized, double-blind trial. Pain 2003;101:193-8. |
|6||Hanks GW, Conno F, Cherny N, Hanna M, Kalso E, McQuay HJ, et al. Morphine and alternative opioids in cancer pain: The EAPC recommendations. Br J Cancer 2001:84:587-93.|
|7||Fortnightly Review: Morphine in cancer pain: modes of administration. BMJ 1996;312;823-6.|
|8||Portenoy RK. Adjuvant analgesics in pain management. In: Doyle D, Hanks GW, MacDonald N, editors. Oxford textbook of palliative medicine. Oxford: Oxford University Press; 1993. p. 187-203.|
|9||Kalso E, Vainio A. Morphine and oxycodone hydrochloride in the management of cancer pain. Clin Pharmacol Ther 1990;47:639-64.|
|10||Hogan Q, Haddox JD, Abram S, Weissman D, Taylor ML, Janjan N. Epidural opiates and local anaesthetics for the management of cancer pain. Pain 1991;46:271-9.|
|11||Harris JT, Suresh Kumar K, Rajagopal MR. Intravenous morphine for rapid control of severe cancer pain. Palliat Med 2003;17:248-56.|
|12||Radbruch L, Loick G, Schulzeck S, Beyer A, Lynch J, Stemmler M, et al. Intravenous titration with morphine for severe cancer pain: report of 28 cases. Clin J Pain 1999;15:173-8.|