Intrathecal Morphine Therapy Research Articles

Opioid-Related Side Effects and Complications After Intrathecal Morphine Trial or Pump Implantation

Objective: A few cases of post-surgical spine syndrome (PSSS) are resistant to standard treatment. Intrathecal morphine (ITM) therapy can be used to achieve improved pain control with fewer side effects compared to systemic analgesics alone. ITM-associated complications may be associated with the intrathecal catheter, implanted pump, device management, and the drugs themselves.Methods: Twenty-six patients with PSSS were retrospectively evaluated. All patients had visual analog scale (VAS) scores of 7 or higher, which continued for more than 6 months, and all received a single dose of the ITM trial. If the VAS score was reduced by 50%, and there were no side effects from the trial, ITM pump (ITMP) implantation was performed for continuous morphine injection to control pain. Of the 26 patients, 19 underwent only the ITM trial, and 7 in whom the VAS decreased by more than 50% after the trial further underwent ITMP implantation. Patients who underwent only the trial were observed for an average of 5.4 days (range: 3–14 days), and those who underwent ITMP implantation were observed for an average of 55.9 months (range: 15–123 months). The occurrence of side effects following ITM injection and complications related to the ITM trial or ITMP implantation were analyzed. Results: The most common complications were drug side effects (n=11), followed by procedural (n=1) and equipment (n=1) side effects. The most common symptoms were urinary difficulty (n=8) and pruritus (n=3). Serious complications included a large lumbosacral subdural hematoma, intradural fibrotic tissues at the lumbar puncture site, and urinary retention (n=1). A case of mid-catheter occlusion caused by precipitated morphine crystals and skin infection on an implantable pulse generator was also reported (n=1). In another case, skin necrosis was observed in the surgical area (n=1). Conclusion: The most common drug-related side effect is urination difficulty, and patients generally recover within a few days after the ITM trial. Complications, such as procedure-related subdural bleeding or IT catheter blockage, may also occur. A better understanding of IT drugs, equipment, and meticulous procedural techniques, can allow a reduction of complications.

Management of patients with pain and severe side effects while on intrathecal morphine therapy: A case study

Background and aimsThe use of intrathecal morphine therapy has been increasing. Intrathecal morphine therapy is deemed the last resort for patients with intractable chronic non-cancer pain (CNCP) who failed other treatments including surgery and pharmaceutical interventions. However, effective treatments for patients with CNCP who “failed” this last resort because of severe side effects and lack of optimal pain control remain unclear. Methods and resultsHere we report two successfully managed patients (Ms. S and Mr. T) who had intractable pain and significant complications years after the start of intrathecal morphine therapy. The two patients had intrathecal morphine pump implantation due to chronic consistent pain and multiple failed surgical operations in the spine. Years after morphine pump implantation, both patients had significant chronic pain and compromised function for activities of daily living. Additionally, Ms. S also had four episodes of small bowel obstruction while Mr. T was diagnosed with end stage severe “dementia”. The successful management of these two patients included the simultaneous multidisciplinary approach for pain management, opioids tapering and discontinuation. ConclusionThe case study indicates that for patients who fail to respond to intrathecal morphine pump therapy due to side effects and lack of optimal pain control, the simultaneous multidisciplinary pain management approach and opioids tapering seem appropriate.

Intrathecal Morphine Therapy for Chronic Non-malignant Pain Using a Constant Flow Infusion System

Background: Implantable pumps for intrathecal opioid therapy in the last decades emerged as one of the most effective treatment for chronic non-malignant pain (CNMP) in selected patients. This study analyses reliability of intrathecal infusion morphine therapy for chronic and refractory pain not related to malignancy using an implantable constant flow pump. Methods: we studied eleven patients (9 women and 2 men; age range 26-67 years), with medically unresponsive CNMP. Pain was classified as neuropathic or non-neuropathic based on clinical features. Patients were evaluated before and after pump implantation, measuring pain intensity and relief after intrathecal opioid treatment based on Visual Analogic Scale (VAS) scores. Results: Pain significantly reduced in almost all patients (91%); mean pain scores improved from 8.9 ± 1.49 before implant to 66% improvement one month after infusion therapy (3.1 ± 1.60) and 41% after 18 months (5.2 ± 2.45). Conclusion: The present data show that intrathecal morphine infusion at a constant flow proved to be a safe and suitable alternative for the treatment of CNMP.

Erfahrungen mit intrathekaler First-line-Therapie mit Ziconotide bei Patienten mit neuropathischen Gesichtsschmerzen

We report on the intrathecal use of ziconotide in three patients with idiopathic facial pain after surgery of the mouth, jaw or face and one patient with neuropathic pain after damage of the lingual nerve. The therapy was successful in three patients but one patient with idiopathic facial pain had pain relief only during the test phase of ziconotide with an external pump and not after implanting the Synchromed® pump. With intrathecal morphine therapy this patient achieved good pain relief. We recommend that patients with neuropathic facial pain should be treated with ziconotide after implementation of guideline-based therapy. In the test phase the ziconotide dose should be increased by 0.6 µg/day per week after an initial dose of 0.6-1.2 µg/day to avoid side-effects.

Spurious urine drug screen results with continuous intrathecal morphine therapy: a case report

Urine drug screening (UDS) has become a common part of the management of patients on chronic opioid therapy. At the same time, the use of implantable intrathecal opioid delivery systems for chronic non-malignant pain has become more popular. There is minimal data in the literature on the use of UDS in patients on continuous intrathecal morphine therapy. This case report highlights the need for further studies in this patient population. A 49 year-old man with continuous intrathecal morphine at 1.448 mg/day for rheumatoid arthritis had a random UDS that was negative for morphine.

Neurosurgery for chronic pain: the main surgical concern should be “anatomical repair” first

It has been the worthy goal of “pain societies” over recent decades to establish, on a multidisciplinary basis, excellent Pain Centers. At present, their networks cover most of the territories belonging to the developed countries. As a neurosurgeon intensively involved in neurosurgery for pain, I am concerned to see a significant number of patients referred for so-called “intractable neuropathic pain,” in whom the pain was not recognized or accepted as resulting from compressive mechanisms. A large number of such painful states belong to tunnel syndromes or radiculopathies/ myelopathies developed in the frame of spondylosis. Some of these correspond to patients who were not operated on but treated for long periods of time with high doses of pain-killers, including anticonvulsants and opioids, or who had repeated local injections of cortisone. The reasons for not having undergone surgery were variable. Of course, there were patients not willing to accept the uncertainty and risks of surgery. There were cases without clear-cut, clinical, laboratory, or imaging criteria for surgery. There were also misleading situations due to multiple (often compressive) pathologies. However, the excessive doggedness of some “pain doctors” in treating chronic pain manifestations instead of their anatomical cause(s) should be deplored. Another group of painful states correspond to patients who were operated on for a pathology but insufficiently. This is particularly true for patients who have undergone so-called minimally invasive procedures. Thus, it is not infrequent to observe the recurrence of symptoms after tunnel syndromes treated with endoscopy. Also, it is rather frequent to see patients with persistent pain after cervical root-spinal cord decompression together with arthrodesis or arthroplasty, in whom the bony resection was not extensive enough; in other words, with the osteophytes still in place in spite of a “nice” X-ray control of the metallic fixation stabilization. Additionally, it is not uncommon to have patients referred for residual pain after lumbar stenoses treated with laminectomy but with too minimal recalibration of recesses and foramens. For all of these patients, before indicating “pain surgery”—especially neurostimulation or intrathecal morphine therapy—reappraisal of the possibility of “remaining compression” should be undertaken. If such a causal mechanism is retained, “anatomical surgery” should be considered first—and proposed—before irreversible neural degeneration occurs.

Low Dose Intrathecal Morphine Therapy and Hypogonadotrophic Hypogonadism

Low Dose Intrathecal Morphine Therapy and Hypogonadotrophic Hypogonadism

Amoxicillin-Associated Hemorrhagic Colitis; Sertraline-Induced Paresthesia; Perioral Dermatitis Associated with an Inhaled Corticosteroid; Aminoglycoside-Induced Hepatotoxicity; Flagellate Dermatitis Seen with Bleomycin; Persistent Hiccups with Intrathecal Morphine Therapy; Sibutramine-Induced Psychosis

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Drug-Related Side Effects of Long-term Intrathecal Morphine Therapy

The introduction of intrathecal opioid administration for intractable chronic non-malignant pain and cancer pain is considered as one of the most important breakthroughs in pain management. Morphine, the only opioid approved by FDA for intrathecal administration, has been increasingly utilized for this purpose. For over 3 decades, there have been numerous reports on the non-nociceptive side effects associated with ever increasing long-term intrathecal morphine usage. To review the literature on side effects due to long-term intrathecal morphine therapy with discussions of alternate treatment options. English-language publications were identified through MEDLINE search and the bibliographies of identified articles were reviewed. Most side effects of intrathecal morphine therapy are dose dependent and mediated by opioid receptors. Common ones include nausea, vomiting, pruritus, urinary retention, constipation, sexual dysfunction, and edema. Less common ones include respiratory depression, and hyperalgesia. Catheter tip inflammatory mass formation is a less common complication that may not be mediated by opioid receptors. The utilization of intrathecal morphine administration for cancer and intractable non-malignant chronic pain represents an important leap forward in pain management. Yet, a wide variety of non-nociceptive side effects may also occur in susceptible patients. The side effects due to intrathecal morphine administration are mostly mediated by opioid receptors. Treatment usually involves the utilization of opioid receptor antagonist, such as naloxone. Patients considering intrathecal opioid pump therapy should be informed and advised about the possible side effects associated with long-term intrathecal morphine administration prior to placement of a permanent morphine infusion pump.

Paraplegia Secondary to Progressive Necrotic Myelopathy in a Patient with an Implanted Morphine Pump

We present an individual with chronic low back pain who was treated with an implanted morphine pump, which provided very good pain relief for 16 mos. However, the patient developed acute paraplegia secondary to progressive necrotic myelopathy, a rare form of transverse myelitis. The cause of this patient's neurologic deficit was unclear. Three months after the onset of paralysis, a trial of discontinuation of the intrathecal morphine was performed to exclude the morphine as a reversible cause of paralysis. Within 24 hrs after his pump was depleted, his pain became significantly worse. He was maintained on oral opioids for 6 mos, and his pain was only partly controlled, with a daily average visual analog scale score of 7/10. There was no improvement in his neurologic status after stopping the intrathecal morphine therapy, and several consecutive magnetic resonance images of the spine demonstrated radiologic progression of spinal cord involvement. The patient developed classic opioid side effects of excessive somnolence and constipation. Intrathecal morphine therapy was re-instituted, and the patient reported a significant decrease of his pain, an improvement in quality of life, and no complications related to pump functioning.

Intrathecal hydromorphone for chronic nonmalignant pain: a retrospective study.

Ten percent to 15% of patients with chronic pain experience intolerable side effects or inadequate analgesia with continuous intrathecal morphine therapy. Although clinical experience suggests that rotation to hydromorphone (Dilaudid) can reduce side effects and recapture analgesia, there have been only scattered reports of long-term intrathecal hydromorphone use in patients with nonmalignant pain. The purpose of this study is to review the safety and effectiveness of continuous intrathecal hydromorphone in the management of patients with nonmalignant pain in whom continuous intrathecal morphine therapy has failed. A retrospective review of 37 patients with chronic nonmalignant pain managed with intrathecal hydromorphone after failure of intraspinal morphine. The mean age of patients was 64 years +/- 12 SD. All patients suffered from severe nonmalignant pain, most from failed lumbosacral spine operations (19/37; 51%). Morphine was replaced with hydromorphone because of pharmacological complications (21/37; 57%) or inadequate analgesic response (16/37; 43%) after an average of 11 months +/- 11 SD of intrathecal therapy. Pharmacological complications, particularly nausea and vomiting, pruritus, and sedation were reduced by hydromorphone in most patients. Peripheral edema was improved by hydromorphone but tended to recur with prolonged hydromorphone exposure. Analgesic response was improved by at least 25% in six of 16 patients who were switched to hydromorphone because of poor pain relief. Hydromorphone can be a safe, analgesic alternative for long-term intrathecal management of nonmalignant pain among patients in whom morphine fails because of pharmacological side effects or inadequate pain relief.

Intrathecal Granuloma in Patients Receiving High-dose Intrathecal Morphine Therapy: A Report of Two Cases

Intrathecal Granuloma in Patients Receiving High-dose Intrathecal Morphine Therapy: A Report of Two Cases

Intrathecal Granuloma in Patients Receiving High‐dose Intrathecal Morphine Therapy: A Report of Two Cases

Intrathecal Granuloma in Patients Receiving High‐dose Intrathecal Morphine Therapy: A Report of Two Cases

Spinal Cord Compression by Catheter Granulomas in High-dose Intrathecal Morphine Therapy: Case Report

Spinal Cord Compression by Catheter Granulomas in High-dose Intrathecal Morphine Therapy: Case Report

Spinal Cord Compression by Catheter Granulomas in High-dose Intrathecal Morphine Therapy: Case Report

Spinal Cord Compression by Catheter Granulomas in High-dose Intrathecal Morphine Therapy: Case Report

Spinal Cord Compression by Catheter Granulomas in High-dose Intrathecal Morphine Therapy: Case Report

Spinal Cord Compression by Catheter Granulomas in High-dose Intrathecal Morphine Therapy: Case Report

Spinal Cord Compression by Catheter Granulomas in High-dose Intrathecal Morphine Therapy: Case Report

Spinal Cord Compression by Catheter Granulomas in High-dose Intrathecal Morphine Therapy: Case Report

Spinal Cord Compression by Catheter Granulomas in High-dose Intrathecal Morphine Therapy: Case Report

Spinal Cord Compression by Catheter Granulomas in High-dose Intrathecal Morphine Therapy: Case Report

Epileptic seizure associated with intracerebroventricular and intrathecal morphine bolus

We report on two patients with morphine-related seizures associated with either intrathecal or intracerebroventricular administration. Both patients had a history of malignant tumor and both experienced the seizures following bolus application of morphine, while even higher dosages were well tolerated when continuously infused. Seizures occurred without signs of intoxication. Initiation of intrathecal morphine therapy and bolus application should be performed carefully and only when constant monitoring is provided for at least 12 h. Animal data and possible mechanisms for morphine-related seizures are discussed.

Cost-effectiveness of long-term intrathecal morphine therapy for pain associated with failed back surgery syndrome

A decision analytic study was conducted using computer simulation to project the outcomes in a simulated cohort of patients whose treatment for back surgery had failed. The objective of this study was to estimate the direct cost of intrathecal morphine therapy (IMT) delivered via an implantable pump relative to alternative therapy (medical management) over a 60-month course of treatment. IMT administered by way of an implantable pump can provide effective pain relief for selected patients whose less invasive treatment modalities have failed. Previous research suggested that a pump implant is less costly than alternative methods providing comparable analgesia for treatment exceeding 12 to 18 months. However, those analyses did not include the cost of complications or pump replacement. Scenarios representing the course of IMT, devised by a panel of experts, were represented as treatment pathways in a Monte Carlo simulation. Adverse event rates were drawn from published data supplemented by expert judgment. Direct costs were based on a health insurer paid claims perspective (direct costs) discounted at a 5% annual rate. The cost-effectiveness of IMT was calculated based on a report of 65% to 81% “good to excellent” pain relief relative to alternative (medical) management. With both adverse event probabilities and costs set at most likely (base case) values, the expected total cost of IMT over 60 months was $82,893 (an average of $1382 per month). In a sensitivity analysis, the best case (low adverse event rate, low cost) estimate was $53,468 ($891/mo), whereas the worst case (high adverse event rate, high cost) estimate was $125,102 ($2085/mo). Cost-effectiveness estimates ranged from $7212 (best case) to $12,276 (worst case) per year of pain relief. Results from a computer simulation designed to collect the costs not included in previous empiric research indicate that IMT appears to be cost-effective when compared with alternative (medical) management for selected patients when the duration of therapy exceeds 12 to 22 months