Pain is prevalent in patients with advanced cancer [1] and is a significant factor underlying an impairment in the quality of life [2]. Cancer-related pain is usually treated in accordance with the World Health Organization (WHO) analgesic ladder. However, about 10% of the patients continue to experience insufficient pain relief or significant adverse effects related to the use of systemic opioids [3].

Intrathecal drug delivery reduces the overall dose and systemic side effects of morphine, and may show better tolerability and efficacy than oral morphine [4]. In addition, it has become an alternative to standard medical management of cancer-related pain. Intrathecal therapy delivers medication directly into the intrathecal space of the spinal column via a catheter connected to an implanted reservoir, which is controlled by a programmable pump [5]. However, in some cases, percutaneous catheter insertion into the intrathecal space could be impeded due to hindrances like existing tumor masses or adhesions from previous surgeries [6].

We describe the case of a patient with intractable pain due to a spine tumor. The patient was treated through intrathecal morphine delivery using an implanted morphine pump.

A 21-year-old female patient was referred to the cancer pain center for pain in her lower extremities, which aggravated one month prior to her visit. The patient was diagnosed with osteochondroma at the 4th lumbar (L4) vertebral body (VB) nine years ago and underwent mass excision several times, followed by posterior lumbar interbody fusion (PLIF) from L3 to L5 VB by orthopedic surgeons. Five years after the last surgery, the tumor recurred at the L3 VB; thus, corpectomy of the lesion was performed. As the tumor was histologically identified as chondrosarcoma (malignantly transformed osteochondromatosis), the patient underwent several sessions of radiation therapy after the surgery.

Three years after radiation therapy, she was admitted with aggravated lower extremity pain. Magnetic resonance imaging (MRI) showed that the chondrosarcoma recurred in the L2–5 VB intraspinal and paravertebral spaces. The patient complained of motor weakness in her left leg since the corpectomy, accompanied by progressive weakness and severe pain in her right leg. Her pain intensity was 8/10 on the 11-point numerical rating scale (NRS) pain score (ranging from 0 = no pain to 10 = worst pain) at rest. Neurological examination revealed motor powers of grade 1 in her lower extremities, and paresthesia and hypesthesia were found in both legs, especially in the right leg. She complained of breakthrough pain with an NRS score of 10/10, which worsened during a position change. At presentation, she was taking pregabalin 150 mg (four times a day) in combination with duloxetine 30 mg (once daily) for the management of neuropathic pain. Medications used for pain management included fentanyl transdermal patch 50 mcg per hour, oral oxycodone 5 mg (four to six times a day), and intravenous fentanyl 50 mcg via patient-controlled analgesia (PCA) (7-8 times a day). We assessed the patient’s pain and increased the dosage of oral oxycodone. After a week, the patient was slightly more comfortable lying in one position with an NRS of 6/10, although her pain would return with an NRS of 10/10 as soon as she tried to move.

The main purpose of treatment was to alleviate the patient’s pain and improve her quality of life. As her life expectancy was more than 12 months, we believed that an externally programmable intrathecal morphine infusion pump (SynchroMed^TM II; Medtronics Minnesota, USA) might be helpful for pain management in this case.

Preoperative MRI showed a large postsurgical pseudomeningocele and dural insufficiency at the previous surgical site (Fig. 1). We co-operated with the orthopedic surgeon to implement intrathecal morphine delivery and pump implantation. The intrathecal catheter used for the procedure was advanced by laminectomy.

Figure 1. Preoperative magnetic resonance (MR) image (sagittal).

Informed consent was obtained from the patient and her parents. All the surgeries were performed under general anesthesia. The patient was positioned in a prone position and aseptic precautions were taken. The orthopedic surgeon performed microscopic surgery for wound exploration and debulking of the pseudomeningocele mass. Next, laminectomy was performed, and the dura was exposed along with the T12-L1 interlaminar spaces. The pain physicians joined the surgery, and the orthopedic surgeon made a microscope-guided dural incision for catheter insertion. The intrathecal catheter was inserted by the pain physician toward the cephalad at the T9 VB level without a stylet. As we could not check the cerebrospinal fluid (CSF) backflow, we used a small volume of contrast medium and checked the intrathecal space by fluoroscopy. The orthopedic surgeon performed dura closure and tight closure of the wound layer by layer, using a microscope. The patient’s position was changed to the right lateral decubitus position with an aseptic drape. A programmable intrathecal pump with a reservoir volume of 20 ml was then placed in the anterior abdominal wall, and the catheter tip was re-identified at the T9 level using fluoroscopy (Fig. 2). The initial dose was kept at 0.8 mg per day, equivalent to 50% of the patient’s morphine requirement of 480 mg equivalents (MME) per day. The pain level after the first 24 hours was 50% of the original value, but it increased to NRS 7/10 again on the second day. Therefore, the intrathecal morphine dose was gradually increased to 3.5 mg/d over a period of 1 week. The intrathecal morphine pump therapy was accompanied by an intravenous pain control system using patient-controlled analgesia (PCA) with oxycodone to manage BTP. With the dose escalation to 5.0 mg/d over 2 weeks, her pain decreased to an NRS of 3-4/10, and BTP was controlled using IV PCA. Finally, the IV PCA was replaced by a fentanyl transdermal patch and oral oxycodone. The patient was discharged with advice to take pregabalin, duloxetine, fentanyl transdermal patch (25 mcg per hour, which is half of the preoperative dose for tapering), and oral oxycodone, in addition to the intrathecal morphine infusion. The refill date of the pump was 1 month after the discharge. The patient was referred to another hospital near her residence for the refill, in consideration of the proximity.

Figure 2. Position of the intrathecal catheter (circle). The tip was located at the T9 vertebra on pain radiography. (A) anteroposterior view. (B) lateral view.

Intrathecal morphine therapy provides pain relief and reduces systemic concerns in patients with cancer-related pain [7]. It is recommended that patients undergo multidisciplinary evaluation before intrathecal pump implantation [8]. Since the Polyanalgesic Consensus Conference (PACC) meeting in 2016, consensus guidelines related to intrathecal therapy for pain relief have been updated to enhance patient safety and decrease the risk of complications [9]. The guidelines recommend morphine and ziconotide as firstline monotherapy for managing cancer-related and non-cancer-related pain [10].

Current data show that 53% patients with cancer experience pain at each stage of the disease, while 58% to 69% of patients experience pain as the disease progresses [10]. Moderate to severe pain is caused either by the tumor itself or by factors related to cancer treatment.

In 2017, a new PACC recommendation confirmed the role of intrathecal analgesia in the management of cancer pain with a high level of evidence (Level I), a strong recommendation (Rank A), and a strong level of consensus [9]. Moreover, it is no longer mandatory to perform a trial before proceeding with permanent implantation (strength I and evidence level III). More recently, the European Society of Medical Oncology (ESMO) published a new recommendation for cancer pain management [11]. They observed that 10% of the patients presented with refractory pain and were recommended intrathecal analgesia. They mentioned that the intrathecal route of opioid administration might be useful for pain below the diaphragm.

Completely implanted devices have a lower risk of infection than percutaneous devices. A permanent intrathecal drug delivery pump can be implanted when life expectancy is more than 6 months [11]. In addition, the European Pain Federation (EFIC) also published new standards [12] for the management of cancer-related pain from the same perspective as the ESMO, and they proposed early referral of patients to a specialized team experienced in invasive techniques such as intrathecal analgesia, before the patient becomes incapable of undergoing supporting surgery. It is no longer necessary to prove intrathecal drug delivery system (IDDS) efficiency for patients with cancer through randomized studies, as this kind of trial appears unethical [13]. Recent publications suggest that IDDS is an efficient procedure for patients with cancer [2,14,15]. Better knowledge of diffusion, research on new drugs for intrathecal therapy, and improvements in the devices will make this procedure more suitable for cancer pain.

However, in some cases, IDDS procedures, including percutaneous catheter insertion into the intrathecal space, might be difficult because of existing tumor or adhesions from previous surgery. However, given the advantages of intrathecal treatment for the management of cancer-related pain, we suggest that intrathecal morphine pumps can be considered for pain control in patients with obstructions from the spinal tumor or previous spinal surgery as well.