|Year : 2018 | Volume
| Issue : 3 | Page : 179-183
A case series discussing the intrathecal drug delivery system to improve the quality of life in terminal cancer patients
Joanna Samantha Rodrigues, Preeti Gupta, Shalini Saksena, Manju Butani
Department of Anaesthesiology and Pain Management, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India
|Date of Web Publication||31-Dec-2018|
Dr. Joanna Samantha Rodrigues
A/11, Landmark, 4th Floor, CHS, Kadamwadi, Vakola, Santacruz (East), Mumbai - 400 055, Maharashtra
Source of Support: None, Conflict of Interest: None
Cancer is a life changing diagnosis and chronic pain in these terminally ill patients is extremely debilitating. In the present case series, the feasibility of continuous infusion of low dose local anaesthetics and opioids through the intrathecal route has been discussed pertaining to patient selection, technique, drugs used and trouble shooting. The intrathecal catheters were connected through a subcutaneous port to an external ambulatory infusion device (CADD pump) and used on a home care basis.
Keywords: Chronic pain, intrathecal route, terminally ill patients
|How to cite this article:|
Rodrigues JS, Gupta P, Saksena S, Butani M. A case series discussing the intrathecal drug delivery system to improve the quality of life in terminal cancer patients. Indian J Pain 2018;32:179-83
|How to cite this URL:|
Rodrigues JS, Gupta P, Saksena S, Butani M. A case series discussing the intrathecal drug delivery system to improve the quality of life in terminal cancer patients. Indian J Pain [serial online] 2018 [cited 2019 Jan 17];32:179-83. Available from: http://www.indianjpain.org/text.asp?2018/32/3/179/249105
| Introduction|| |
The introduction of intrathecal drug delivery systems has been considered as one of the most important breakthroughs in pain management in the past three decades for patients with chronic and cancer pain. The delivery of drugs into the intrathecal space provides superior analgesia with smaller doses of analgesics. Intrathecal analgesia is an option available for patients who are unable to tolerate conventional opioid therapy to provide pain relief and improve quality of life. Intrathecal system options range from connecting a tunnelled intrathecal percutaneous catheter to an external pump or a totally implanted system. Choice depends on factors including, life expectancy, cost and availability of medical expertise and patients comfort level. Both type of pumps can be refilled periodically utilizing a sterile technique. We present five cases in which this therapy was employed to tackle the dynamic pain in terminal cancer patients in the Indian scenario. Patients in this case series were counselled and explained about the procedure and relevant informed consents were procured.
| Case Reports|| |
A 56-year-old woman with intractable left thigh pain due to recurrence of osteosarcoma of the femur was referred to our clinic. She was unable to tolerate oral morphine or fentanyl patch due to intense nausea and vomiting. Therefore, she was evaluated for intrathecal drug delivery (ITDD). She underwent psychological evaluation confirming her candidacy and she was scheduled for a permanent intrathecal (IT) port implantation using VYGON Minisitimplant [Figure 1]. The catheter was placed in the IT space at L4-L5 level and the catheter tip advanced to L2, under fluoroscopic guidance [Figure 2]. Satisfactory catheter placement was confirmed by dye study [Figure 3]. The proximal tip of the catheter was then tunneled [Figure 4] subcutaneously and connected to the implantable port, which was placed in a subcutaneous pocket in the anterior abdominal wall on the right side [Figure 5]. Using a 22G port needle, the IT system was connected to the continuous ambulatory drug delivery (CADD) pump and reservoir bag of 250 ml containing preservative-free morphine 25 mg (concentration of 0.1 mg/mL) and ropivacaine 0.15% (concentration of 1.5 mg/mL). The pump was programmed to deliver a basal rate of 0.3 mL/h with the on-demand bolus dose of 0.5 mL and a lockout interval of 240 min. The patient was then instructed how to use the pump and was discharged home.
The patient required the on -demand bolus dose. The infusion delivered was approximately 9.2–10 mL/day with 0.92–1-mg morphine daily. The infusion lasted 7 months. The daily morphine requirement increased to 1 mg toward the end of life. The patient reported more than 90% pain reduction with improved distance for ambulation. She did not experience any other significant adverse events during this ITDD.
A 60-year-old male was admitted to hospital with renal cell carcinoma with severe buttock and coccyx pain due to metastasis to the sacrum and sacroiliac joint with sacral insufficiency fracture. A variety of oral medications had been previously prescribed including slow-release morphine up to 60 mg twice daily and various adjuvants such as nonsteroidal anti-inflammatory agents and tricyclic antidepressants over a 1-month period with minimal control of pain. IT port was inserted and refilled with 0.15% ropivacaine and 25 mg of morphine in 250-ml normal saline. The patient was discharged home after experiencing more than 80% pain relief with a basal rate – 0.4 ml, bolus dose – 0.5 ml, and lockout period of 4 h. This patient survived 3 months with IT pain relief.
A 49-year-old male was admitted to the hospital with a sacral myxopapillary ependymoma with liver metastasis and radicular compression of sacral nerve roots. He complained of severe pain in the left leg. Following a psychological evaluation confirming his candidacy, he underwent patient-controlled epidural ropivacaine and morphine infusion trial. A week later, after the patient reported more than 90% pain reduction with improved distance for ambulation, he was scheduled for a permanent IT port implantation. The patient was discharged with good pain relief following the procedure. He presented 2 months later with external migration of the IT port from the anterior abdominal wall due to increase in ascites. This was refashioned and the pump was continued. The patient lived for 5 months using the spinal analgesia.
A 59-year-old male having a pelvic chondroma and compression of sacral nerve roots presented to the hospital with severe back pain and bilateral lower limb pain. The patient underwent a successful trial with subarachnoid block using 1 ml of 0.75% ropivacaine and 25-mcg fentanyl. The IT port was inserted with an infusion of ropivacaine 0.15% and morphine 25 mg at an infusion rate of 0.2 ml/h with a bolus dose of 0.5 ml/h and a lockout period of 240 min. He was discharged with good pain relief but expired within 3 weeks after implantation.
A 37-year-old woman with breast cancer and liver metastasis presented with right hypochondriac pain. Despite high oral and topical opioids, her pain scores were 8–9/10. An IT port was implanted with ropivacaine 0.15% and morphine 25 mg in 250-ml normal saline. She received a continuous infusion dose of 0.4 ml/h with a bolus dose of 0.4 ml/h and lockout time of 240 min. She was discharged with good pain relief and increased distance of ambulation. A refill was done at 3 weeks after the insertion. However, she passed away 2 days later.
| Discussion|| |
The rising trends of cancer both in the rural and urban population of our country have commanded us to devise a strategy to identify pain- related to the disease process, its treatment and a robust approach to tackle it and provide relief in the terminally ill cancer patients. In this series, the technique to alleviate pain was through ITDD systems controlled by CADD pumps.
These five patients were chosen for ITDD therapy due to significant side effects from oral and transdermal opioids which did not allow titration of these agents to adequate analgesia. The success of this therapy lies in proper patient selection and preprocedure counseling and evaluation [Table 1]. All our patients had pain restricted to certain part of the body and were cooperative despite being uncomfortable in excruciating pain. They underwent physical examination, blood tests, electrocardiogram, and chest X-rays. The recent positron emission tomography and computed tomography scans were reviewed. They were not eligible for any more treatment options for cancer cure. Ongoing systemic anticoagulants and antiplatelet therapies were discontinued. Antibiotic prophylaxis was administrated to all the patients. Under monitored anesthesia care and complete sterile precautions, the IT catheter was placed at the desired spinal level under fluoroscopy guidance. The catheter was then tunneled and connected to the port placed surgically under the skin in the anterior abdominal wall. The port was connected to the reservoir bag (CADD cassette) through the port needle inserted percutaneously [Figure 6]. The pump was programmed to deliver continuous rate and bolus dose with a lockout interval for breakthrough pain. The IT catheter and subcutaneous port placement was done by our chronic pain team. The choice of drug, concentration, and sterile periodic refilling of the CADD pump was also done at our pain clinic.
The choice of medication was dependent on the success of our past and present medication choices, and we decided to use morphine along with ropivacaine, both of which are available preservative free. IT ropivacaine was considered initially in experimental studies as it does not markedly interfere with spinal cord blood flow. Ropivacaine is known to have a better sensory blockade rather than a motor blockade [Table 2]. Studies have indicated that ropivacaine promotes the effects of IT opioids as well.
ITDD provides continuous infusion of the drug in the cerebrospinal fluid. Only small amounts are required as compared to the higher doses taken orally, intravenously, transdermally, or through epidural administration. It can also be used to alleviate noncancer pain [Table 3]. The long-term efficacy of IT opioid medications for cancer pain is substantially more than its systemic application as intrathecally opioids exert a strong analgesic effect through spinal receptors without significantly influencing motor, sensory, and sympathetic reflexes. All the five patients had improvement in dynamic pain and were able to ambulate. They had overall improvement in mood and quality of life and ability to participate in daily activities till the end of life.
|Table 3: Recommended starting dosage ranges of intrathecal medications for long-term therapy delivery|
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Along with allaying the pain, it is also pertinent to mitigate the complications due to this technique and minimize the damage control in the already agonized patients. Any complication needs immediate hospitalization, careful diagnosis, and sensitive management as they are quite serious and often fatal. A retrospective study by Krakovsky showed that most common complication encountered was an adverse reaction to the drug itself. Serious complications include respiratory depression/arrest, anaphylaxis, and meningitis with introduction of contaminated solution [Table 4]. Some complications are specific to certain drugs, for example, catheter tip granulomas which were more frequent with morphine than fentanyl – a disadvantage which helped fentanyl to be upgraded as a first-line drug in the algorithm. Catheter and pump related malfunctions may be encountered though not encountered in this case series [Table 5]. Procedure-related complications include subcutaneous tissue necrosis and loss of device, especially in patients with low subcutaneous fat, small abdominal area, or atrophic (cortisone) skin. Instrument-related complications arise from faulty programming of the instrument or due to instrument failure or battery failure. We fortunately experienced no infection in the five cases that we inserted the IT pump. One patient came with exteriorization of port due to increase in abdominal girth, related to ascites. New deeper subcutaneous pocket was created and the pump went on smoothly until the end of life. Adherence to guidelines and following the recommendations for surgical site infections helps to dip the infection rate.
|Table 4: Drug-related adverse reactions to mediations delivered through intrathecal drug delivery|
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Trialing was previously considered crucial in predicting a patient's response to the IT treatment. However, this has been challenged by the PACC 2012 expert panel and was considered debatable specifically in cancer pain patients. The main aim of trialing is to determine whether port implantation should proceed. Several neuraxial techniques are used for trialing of IT therapy. They could be IT or epidural, bolus, or continuous doses and various combinations of different doses, treatment duration, and catheter/injection placement. Trialing can be valuable to obviate pain while leaving the catheter in place till the permanent IT pump is implanted. However, a single-shot trial or an infusion of 72–96 h cannot satisfactorily answer the pain relief or even present the potential side effects. Still, these trials are being performed on the basis that they mimic the system that would eventually be implanted. We trialed two cases in which we were doubtful about the dermatomal level of pain to be targeted. We used an epidural catheter in one and an IT single-shot drug in another. In the other three patients, we were certain about the benefits of the permanent implant.
This brings us to the quintessential question regarding the feasibility of this procedure in an economically challenged country as well as the justification of using this pump in terminal cancer patients with life expectancy of <3 months. Cancer survival is difficult to predict and it is well known that treating cancer pain adequately improves life expectancy. We used an IT port with external reservoir for drug delivery instead of a fully implanted programmable pump. This helped reduce the cost while maintaining the option of bolus dosing during episodes of increase in pain. Despite the upfront cost, the maintenance costs over time are significantly lower than conventional oral/topical opioid therapy. The risk of infection was explained to all our patients but maintaining hygiene and sterile transparent occlusive dressing at the port needle site and helped minimize the risk. Although two of our patients lived only 3 weeks after placement of IT pump, their families were satisfied despite the cost involved and agreed that it was the treatment of choice in providing pain relief, especially when treatment options for treating cancer had failed.
| Conclusion|| |
No doubt the treatment of pain poses an ongoing challenge to the health-care field and better prevention, assessment, and treatment of pain is needed. ITDD using the external reservoir is a simple, safe, and effective option for treating cancer pain and improving survival with better quality of life. This procedure can be performed under fluoroscopic guidance at primary care centers without surgical expertise. This is a robust system for providing pain relief in the terminally ill cancer patients at home, along with supervision from home-care nurses and education of caregivers.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]