Abstract
Buprenorphine is a frequently used opioid in the treatment of neuropathic pain component that is often present in patients with cancer. A case of a 41-year-old patient was depicted whose pain syndrome was associated with the chondrosarcoma growth originating from the sacral bone and numerous surgical interventions and radiotherapy. Improvement in analgesia and good toleration of therapy were observed after switching from transdermal fentanyl to transdermal buprenorphine while maintaining treatment with antidepressants and anticonvulsants. This case report indicates a possibility of a safe switch of transdermal opioids at home, which may provide benefits in terms of analgesia and adverse effects and in consequence have positive impact on the patients’ quality of life. This is also accompanied by constant psychological, social, and spiritual support provided to the patient and family.
Keywords
Introduction
In Poland, buprenorphine is one of the most commonly used opioids in patients with cancer with moderate to severe pain intensity 1 and in other chronic no-malignant pain syndromes. 2 Currently, the drug is most commonly used in a convenient formulation of transdermal patches applied on the intact skin usually every 3.5 days (twice a week). 3 High analgesic efficacy of buprenorphine was also proven in patients with neuropathic pain component. 4 Apart from significant analgesic efficacy, the drug is usually well tolerated. 5 Although buprenorphine is a partial μ-opioid receptor agonist in the therapeutic dose range used in patients (up to 140 μg/h, which equals approximately a dose of 3.2 mg/24 h), the drug displays activity similar to pure opioid receptor agonists. 6 –8 The treatment is usually commenced with low doses (17.5-35 μg/h) titrated to satisfactory analgesia and acceptable adverse effects. It allows to safely combine buprenorphine patches with other opioids administered in breakthrough pain episodes (immediate-release morphine, fentanyl nasal spray, or buccal tablets). 9 –12 Buprenorphine is an opioid, similar to fentanyl, recommended for patients with renal impairment and during dialysis. 13 In contrast to morphine, buprenorphine does not display a significant immunosuppressant effect. 14,15 Analgesic effects of buprenorphine are independent of P-glycoprotein expression, a protein responsible for drug transport through the blood–brain barrier which influences morphine analgesia. 16
Fentanyl belongs to opioid analgesics that display agonist effects on μ-opioid receptors. It has been successfully used for 15 years in Poland in transdermal patches in the treatment of chronic pain syndromes of different etiology, including patients with cancer. Thanks to its high lipophilicity, fentanyl exerts mainly central effect that may explain less impact on gastrointestinal tract function, for example constipation, nausea, and vomiting, in comparison to hydrophilic opioids such as morphine; however, in contrast to buprenorphine, fentanyl does not inhibit hyperalgesia development. 17 Up to date, Polish experience with buprenorphine. 18,19 saw no patients who had changed from transdermal fentanyl to transdermal buprenorphine. The aim of this case report is therefore to depict transdermal fentanyl to transdermal buprenorphine rotation in a patient with neuropathic pain syndrome.
Case Presentation
A 41-year-old patient diagnosed with chondrosarcoma (histological malignancy grade G2) located in the sacral bone, after numerous surgical interventions and radical radiotherapy, has been experiencing pain since Spring 2006 in the right sacral region radiating to the right lower extremity of neuropathic characteristics. In September 2006, a magnetic resonance imaging revealed a tumor in the lumbo-sacral region. A local tumorectomy was conducted in October 2006; in April 2007, due to a local recurrence tumorectomy was performed again—both from posterior access. In October 2007, next tumor recurrence was diagnosed. A 2-step surgery was conducted: first, from anterior access a ligation of iliac internal artery and incision of the sacral bone cortex lamina with a margin around the tumor; second, from posterior access, a partial resection of the sacral bone on the right side and lumbopelvic stabilization.
In October 2009, yet another surgery (a cytoreduction of the tumor) was performed due to a local tumor recurrence. In April and May 2010, the patient underwent a radiotherapy course (photons, total dose 40 Gy on the sacral region). Further radiotherapy (30 Gy the same field) was performed in June and July 2010. In August, the patient was admitted to the hospital for blood transfusion (4 units of red blood cells) due to anemia. In September and October 2010, the symptoms of postirradiation colitis appeared (diarrhea). In November 2010, the patient was admitted to the hospital as a result of urinary tract infection, diarrhea, electrolyte imbalance, and fistula of the surgery scar in the sacral region.
In the period from December 2010 until February 2011, the patient underwent surgery in the National Centre of Spine Diseases Treatment in Budapest; in December colostomy was exposed; in January 2011 a total tumor resection was conducted with sacropelvic stabilization, skin, and subcutaneous tissue plasticity with transplantation of skin–muscle flaps to cover the defect. A difficulty in wound healing proved to be a surgical complication due to a necrosis of muscle flaps transplants and skin fistula in the postoperative wound. From February to March 2011, the patient stayed in a hospital and underwent 3 surgical interventions in order to elaborate postoperative wound and hypotension therapy. In July 2012, another surgery was performed for the resection of fistulas in the scar after plasticity of the rotated skin flap, skin plasticity, and hypotension therapy of the pressure sore in the region of sciatic tuber at the right side were conducted. In November and December 2011, the patient underwent therapy in the hypobaric chamber, with a significant decrease in exudate and partial closure of the skin. Currently, investigations do not reveal any signs of the tumor relapse.
Pain in the lumbar spine radiating to lower extremities of neuropathic characteristics significantly intensified in 2008. In February 2009, the patient was admitted to our Outpatient Palliative Medicine Clinic. After palliative medicine specialist consultation at home as a result of severe pain intensity (NRS 8), the patient was admitted to a palliative care unit. The following drugs were prescribed: transdermal fentanyl 25 μg/h every 72 hours, controlled-release morphine 100 mg twice daily; in case of breakthrough pain 15 to 30 mg immediate-release morphine, diclofenac 100 mg once daily, venlafaxine 75 mg once daily, metoclopramide 10 mg 3 times daily, omeprazol 20 mg once daily, baclofen 25 mg 3 times daily, carbamazepine 150 mg twice daily, and lactulose 7.5 g 3 times daily. Analgesia improved (NRS 4-5) and the treatment was well tolerated. After discharge carbamazepine was substituted with pregabaline at a dose of 75 mg twice daily. The treatment was continued until the end of 2010.
In April 2011, after returning home, the patient continued the same medications with the exception of diclofenac, omeprazol, baclofen, and regular controlled-release morphine; the patient was prescribed 10 to 20 mg of immediate-release morphine for breakthrough pain and regular paracetamol at a dose of 500 mg 3 times daily. In September 2011, pain intensified (NRS 6) and the patient asked about changing pain medications. After discussion with the patient, it was decided that the fentanyl patch 25 μg/h will be changed to transdermal buprenorphine at a dose 35 μg/h twice a week. Accordingly, analgesia improved (NRS 4) with satisfactory toleration of the treatment and it was possible to stop paracetamol administration. After several months, due to a slight increase in pain intensity (NRS 5), the dose of buprenorphine patch was increased to 52.5 μg/h and satisfactory analgesia was achieved (NRS 3).
Currently, the patient continues the treatment without significant adverse effects. In spite of colostomy, lactulose needs to be administered to render regular bowel movements. The patient complained for several months about excessive sedation that limits mental activity during the day. After rotation from fentanyl to buprenorphine, the drowsiness decreased; however, with the current dose of buprenorphine it is similar to that from the period of fentanyl treatment. The patient claims that this problem appears especially after administration of immediate-release morphine. For breakthrough pain episodes, the first-line treatment is paracetamol at a dose of 500 mg; when this fails, 20 mg of immediate-release morphine is administered. The patient undergoes regular rehabilitation program due to the paresis of lower extremities. Daily changes of sterile dressing and octenisept are needed due to the exudate from the postoperative wound. Currently, the urine divertion is possible thanks to external catheter that substituted internal catheter placed in the bladder. The fistula in the left buttock is healing and is currently treated with 10% sodium chloride.
Discussion
The depicted patient is an example of complex problems related to former tumor development, numerous surgical interventions that in most cases were nonradical, and complications associated with the treatment. Additional factors include patient’s young age, immobility, and pain syndrome, which developed following radical surgery and radiotherapy. Apart from the members of the home palliative care team (physician, nurse, physiotherapist, and psychologist) and orthopedist specializing in spine surgery and in oncological orthopaedics, family members who are physicians have been actively involved in the care for the patient. Thanks to that, the patient may stay at home with his wife—a physician radiologist and a 4.5-year-old daughter. A significant support for the patient is the possibility to meeting with a roman-Catholic priest. For a few years now (after the second surgery), the patient has been unable to walk and stays in bed; it is necessary to change the dressing everyday. In spite of the lack of recurrence in current imaging investigations, his prognosis is uncertain due to complications after extensive surgery and radiotherapy and the possibility of tumor relapse.
One of the main problems of the patient is the neuropathic pain syndrome. The patient depicts pain as a “skin hyperalgesia” in lower extremities with a periodical sensation of “electric current.” According to the patient’s depiction pain is still present; however, thanks to the medications, it is “significantly suppressed.” The cause of the pain is nervous system damage resulting from numerical and extensive surgical interventions and radiotherapy; formerly, it was also evoked by the tumor growth. An effective pain treatment is possible, thanks to the combination of an opioid (buprenorphine). 20 with coanalgesics (venlafaxine, pregabaline). 21 The adverse effect of such combination is drowsiness, especially in the morning. 22 However, during our visits the patient is fully alert, with logical contact and no signs of cognitive impairment. Recently, the patient started the treatment with methylphenidate 5 mg once daily to decrease sedation. 23 In spite of headache and nausea and partial effect (sedation decrease by 30%), the therapy is continued.
Higher effectiveness of the treatment with buprenorphine in comparison to fentanyl should be emphasized here. Analgesia improvement may be ascribed to better analgesic efficacy of buprenorphine in neuropathic pain component 24,25 due to the suggested antihyperalgesic effect of the drug, 26 higher buprenorphine dose, and too low fentanyl dose. The first reason seems to be mainly responsible for the benefits of the treatment; apart from the positive assessment of analgesia by the patient himself, an indirect proof is the possibility of the withdrawal of regular paracetamol administration during buprenorphine treatment. The treatment with adjuvant analgesics remained unchanged compared to the fentanyl treatment period. Attention should be drawn to the lack of adverse effects during opioid rotation and the necessity of only one dose increment during over a 12-month period of buprenorphine treatment. Local skin reactions appear slightly more frequently during buprenorphine compared to fentanyl treatment, but the patient did not report skin reactions during buprenorphine therapy. 27
There is a lack of controlled studies concerning rotation from transdermal fentanyl to buprenorphine patches or in the opposite way. Mercadante et al conducted a study in patients with cancer with pain; however, this trial was a short-term study (after 3 days from the opioid change patients were rotated back to the former opioid). In contrast to our study that study concerned patients with effective analgesia, observed before switching from fentanyl to buprenorphine or the opposite. 28 However, our dose ratio calculation was based on Mercadante et al, that is, fentanyl dose of 25 μg/h equaled buprenorphine dose of 35 μg/h. Such dose ratio seems to be effective and safe but should be verified in well-planned, prospective clinical studies.
Apart from analgesic effects other factors influencing the fate of opioids in treated patients such as clinical status of patients, opioid adverse effects, comorbidities, and concurrent use of other medications may impact opioid’s equianalgesic dose ratio. Several studies suggest similar or stronger analgesic effect of transdermal buprenorphine compared to transdermal fentanyl. 29 –31 Own experience indicates that when buprenorphine fails as an analgesic, it is possible to safely and effectively rotate to another opioid immediately, without the 24-hour delay suggested by the product characteristics. 32
In summary, transdermal buprenorphine with adjuvants rendered satisfactory analgesia with acceptable adverse effects. A holistic care at home provided by the interdisciplinary team allows to benefit from medical aid, psychosocial and spiritual support, and to improve patient and family quality of life.
Footnotes
Declaration of Conflicting Interests
The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author received no financial support for the research, authorship, and/or publication of this article.