Intrathecal Drug Delivery Systems Research Articles

Evaluation of intrathecal drug delivery system for intractable pain in advanced malignancies

Pain is prevalent in advanced malignancies; however, some patients cannot get adequate pain relief by conservative routes of analgesic administration or experience serious side effects related to high dose of opioids. For those who have exhausted multimodal conservative analgesic, intrathecal drug delivery is an alternative intervention for truly effective pain management. The objective of this study was to evaluate the clinical efficacy and safety of intrathecal drug delivery system (IDDS) for the treatment of intractable pain in advanced cancer patients.A prospective cohort study was performed between July 2015 and October 2016. Fifty-three patients undergoing intractable cancer-related pain or intolerable drug-related adverse effects were recruited and received IDDS therapy with a patient-controlled intrathecal analgesia pump. The assessment was conducted during admission, in titration period, and followed up monthly to death by scheduled refill visits. Pain numeric rating scale scores, comprehensive toxicity scores, quality of life scores, systemic opioid use (basal and breakthrough dose), intrathecal morphine use (basal and patient-controlled intrathecal analgesia dose), and complications were recorded to evaluate the curative effect and safety.Between baseline and all subsequent follow-ups, statistically significant decreases in pain numeric rating scale scores and comprehensive toxicity scores were verified. A statistical improvement in quality of life scores was found after starting IDDS therapy. Both basal and breakthrough doses of systemic opioid showed a significant decrease during the follow-up period. And there was a modest escalation in the intrathecal morphine dose throughout the duration of study. No infective, device-related, and catheter-related complications were observed.The findings showed that IDDS therapy allowed for rapid and highly effective pain relief with less toxicity in comparison to conservative medications. Patients with advanced malignancies would also benefit from an improvement in the life quality after the procedure. IDDS therapy represented a valuable option for intractable cancer-related pain management.

New Cancer Pain Treatment Options.

Cancer pain is often incapacitating and discouraging to patients; is demoralizing to family members and care takers; and is taxing and difficult to subdue for the pain specialists. The consequences of implementing suboptimal treatment are far-reaching; therefore, effective treatment methods are in a great demand. The face of cancer pain management has changed in considerable ways, and interventional procedures have become an integral part of providing multimodal analgesia in cancer pain treatment. The goals of this review are to draw attention to the critical role that regional anesthetic nerve blocks and interventional pain management techniques play in treating malignancy-related pain and emphasize the benefits provided by the aforementioned treatment strategies. A large proportion of cancer patients continues to struggle with an inadequately treated pain despite a strict adherence to the WHO analgesic step ladder. The previous pain treatment algorithm has been modified to include peripheral neural blockade, neuro-destructive techniques, neuromodulatory device use, and intrathecal drug delivery systems. The accumulated evidence highlights the opioid-sparing qualities and other benefits afforded by these modalities: decreasing medication-induced side effects, reducing economic burden of poor analgesia, and overall improvement in quality of life of the patients afflicted with a painful neoplastic disease. The rising prevalence of cancer-related pain syndromes is paralleled by an unmatched growth of innovative treatment strategies. Modified WHO analgesic ladder represents one of the greatest paradigm shifts within the domain of oncologic pain treatment. The cancer patient population requires a prompt and liberal, albeit judicious, delivery of unorthodox pain treatment options freed from the rigid bonds of conventional guidelines and standard practices.

Influence factors of intrathecal drug delivery systems for chronic intractable pain

Background Implantable drug delivery systems (IDDS) is an effective option for the treatment of chronic intractable pain. However, not all patients can achieve ideal effect in clinical application. Objective To summarize the factors that affect chronic pain patients' IDDS, and provide new methods and ideas for clinical practice. Content Proper patient selection, drug selection and management are very important for the IDDS analgesia. The position of the catheter tip, choice of drug, transmission model and so on influence the IDDS analgesic effect. Trend Patients with chronic pain treatment requirements are constantly improve, therefore, application of IDDS will provide effective analgesia for patients with chronic intractable pain. The progress in pharmacokinetic of cerebrospinal fluid, drugs for intrathecal injection, implantation procedure, good perioperation management and so on will improve the effects of IDDS. Key words: Intrathecal injection; Chronic pain; Analgesics, opioid; Cerebrospinal fluid

Intrathecal Catheter Insertion and Analgesia is a Safe and Effective Method of Pain Control in Patients with Advanced and Intractable Cancer Pain

Introduction: Pain affects the quality of life in cancer patients. The World Health Organization established a simple three-step “ladder” approach in 1986, beginning with nonopioid drugs and progressing to stronger opioids as necessary. The implementation of this guideline enables analgesia to be achieved in 75% to 90% of patients. The remaining patients suffer from intractable pain requiring intrathecal analgesia. Advances in intrathecal analgesia and intrathecal drug delivery systems have allowed for a range of medications to be used in the control of pain in the remaining 20% of patients with intractable cancer pain. This technique allows for reduced medication doses that can decrease the side effects typically associated with oral or parenteral drug delivery. We aim to analyse the pain intensity before and after intrathecal analgesia and review the complications associated with the implantation and the care of the intrathecal device. Materials and Methods: We retrospectively analysed medical records of all cancer patients whose pain were managed by intrathecal catheter implants in our centre from February 2005 to December 2014. The pain intensity was reviewed at the time prior to administration of intrathecal analgesia and at physician review prior to hospital discharge or death. Complications related to intrathecal analgesia were reviewed from the patients’ medical records. Results: We analysed the data obtained from 44 patients. 86.4% had metastatic cancer. Pain intensity was reduced significantly at the time of discharge from hospital (P<0.001). Opioids side effects were reduced after intrathecal treatment. The main catheter-related complications were catheter displacement and infection. Conclusion: Intrathecal catheter insertion and analgesia is a safe and effective method of pain control in patients with intractable cancer pain.

Intrathecal Drug Delivery Systems (IDDS): The Implantable Systems Performance Registry (ISPR)

ObjectivesThe ISPR was initially created to monitor the product performance of Medtronic implanted intrathecal drug infusion and spinal cord systems available in the United States.Materials and MethodsData were collected from 50 representative sites implanting and following patients with intrathecal drug delivery systems across the United States between August 7, 2003 and January 31, 2014. Device performance over time was estimated using life table survival methods.ResultsOf the 6093 patients enrolled in the ISPR, 3405 (55.9%) were female and 2675 (43.9%) were male, and 13 (0.2%) did not provide gender data. The average age at enrollment was 52.9 years (SD =17.6 years) and average follow‐up time was 29.6 months. Currently, the estimates of device survival from pump‐related events exceed 90% for all pump models across the applicable follow‐up time points. The majority of product performance events were catheter‐related. At 5 years of follow‐up, all applicable catheter models, with the exception of revised not as designed or grafted not as designed catheters, had greater than 81% survival from catheter‐related events.ConclusionsThe ISPR is designed to serve as an ongoing source of system and device‐related information with a focus on “real‐world” safety and product performance. ISPR data continue to be used to guide future product development efforts aimed at improving product reliability and quality.

Surgical Site Infections in Cancer Patients with Intrathecal Drug Delivery Devices.

Our purpose was to determine the incidence of surgical site infection (SSI) in cancer patients receiving an intrathecal drug delivery system (IDDS) and compare that rate with the incidence of SSI in the general population receiving an IDDS or spinal cord stimulator. We attempted to describe risk factors for SSIs in cancer patients treated with IDDS in terms of exposure to cancer treatments. Retrospective review. Large tertiary care center. Cancer patients receiving an IDDS in 2006-2013. The incidence of SSI was determined according to the US Centers for Disease Control and Prevention definition. Medication regimens and current cancer treatment were investigated to identify immunocompromised patients during IDDS placement. Microbacteriology, treatment, and overall outcomes were investigated. Sixty-four patients had an IDDS implanted in 2006-2013. SSI developed in four patients (6.2%). All four patients had received chemotherapy or radiotherapy within three months before implantation. Three of the three were receiving dexamethasone, and three of the four required explantation of the IDDS. The incidence of SSI was at the upper end of the published infection rates for IDDS. The risk of SSI may be increased in this population because of factors that alter the patient's immune status, including concomitant corticosteroid use, radiotherapy near the SSI, and presence of immunomodulators. The identification and mitigation of certain risk factors for this population may prevent infection in future patients.

Treatment of Refractory Postdural Puncture Headache after Intrathecal Drug Delivery System Implantation with Epidural Blood Patch Procedures: A 20-Year Experience.

A recent publication reported the incidence of postdural puncture headache (PDPH) in conjunction with intrathecal drug delivery system (IDDS) implantation to be nearly 23 percent. Many patients responded to conservative measures but a percentage needed invasive treatment with an epidural blood patch (EBP). There is limited data to describe the technical details, success rates, and complications associated with EBP in this population. This study aims to provide a retrospective report of EBP for patients suffering from PDPH related to IDDS implantation. A chart review established a cohort of patients that required EBP in relation to a PDPH after IDDS implantation. This cohort was evaluated for demographic data as well as details of the EBP including technical procedural data, success rates, and complications. All patients received a trial of conservative therapy. Standard sterile technique and skin preparation were utilized with no infectious complications. The EBP was placed below the level of the IDDS catheter in 94% of procedures. Fluoroscopy was utilized in each case. The mean EBP volume was 18.6 cc and median time of EBP was day 7 after implant. There were no complications associated with EBP. EBP appears to be an effective intervention in this subset of PDPH patients.

Upper Antero-Medial Thigh as an Alternative Site for Implantation of Intrathecal Pumps: A Case Series

Neuraxial drug delivery via intrathecal drug delivery systems (IDDS) is becoming an increasingly common mode of treating intractable cancer-related pain, chronic pain, or severe spasticity. An implanted infusion pump delivers medication into the intrathecal (subarachnoid) space via a thin catheter. These pumps are commonly placed in the anterior abdominal wall. Certain conditions may render it difficult or unsafe for an IDDS to be implanted at the traditional site; thus, alternative sites have been explored. We report on the use of the upper antero-medial thigh as a safe alternative site for this purpose. Nine patients between 22 and 69 years of age underwent placement of an IDDS infusion pump in the upper antero-medial aspect of one thigh. In each patient, the anterior abdominal wall was precluded for implantation due to various reasons, such as extensive abdominal scar tissue from previous surgeries, placement of feeding tubes and ostomies, large ventral hernia or metastatic masses protruding from the abdomen. Nine patients, with ages ranging from 22 to 69 years old, had IDDS implantation in the upper thigh. The first patient experienced wound dehiscence (antero-lateral location) and after explantation, another pump was placed successfully in the opposite thigh (antero-medial location). One patient has had pump replacement due to end-of-battery life. She also needed an unrelated catheter revision. Seven patients have expired from their disease progression after living for an average of 142.7 days (range 50 days to 354 days) while two patients continue to experience relief from pain and spasticity years later (see Table 1). No neurovascular damage, infections, or other complications occurred in our series. The upper antero-medial thigh is a safe alternative to the anterior abdominal wall for implantation of an IDDS.

High-Resolution Three-Dimensional Computed Tomography for Assessing Complications Related to Intrathecal Drug Delivery

Background: The assessment of the functionality of intrathecal drug delivery (IDD) systems remains difficult and time-consuming. Catheter-related problems are still very common, and sometimes difficult to diagnose. Objectives: The aim of the present study is to investigate the accuracy of high-resolution three-dimensional computed tomography (CT) in order to detect catheter-related pump dysfunction. Study Design: An observational, retrospective investigation. Setting: Academic medical center in Germany. Methods: We used high-resolution three dimensional (3D) computed tomography with volume rendering technique (VRT) or fluoroscopy and conventional axial-CT to assess IDDrelated complications in 51 patients from our institution who had IDD systems implanted for the treatment of chronic pain or spasticity. Results: Twelve patients (23.5%) presented a total of 22 complications. The main type of complication in our series was catheter-related (50%), followed by pump failure, infection, and inappropriate refilling. Fluoroscopy and conventional CT were used in 12 cases. High-resolution 3D CT VRT scan was used in 35 instances with suspected yet unclear complications. Using 3D-CT (VRT) the sensitivity was 58.93% – 100% (CI 95%) and the specificity 87.54% – 100% (CI 95%).The positive predictive value was 58.93% – 100% (CI 95%) and the negative predictive value: 87.54% – 100% (CI 95%). Fluoroscopy and axial CT as a combined diagnostic tool had a sensitivity of 8.3% – 91.7% (CI 95%) and a specificity of 62.9% – 100% (CI 95%). The positive predictive value was 19.29% – 100% (CI 95%) and the negative predictive value: 44.43% – 96.89% (CI 95%). Limitations: This study is limited by its observational design and the small number of cases. Conclusion: High-resolution 3D CT VRT is a non- invasive method that can identify IDDrelated complications with more precision than axial CT and fluoroscopy. Key words: Volume rendering technique (VRT), intrathecal drug delivery systems, highresolution 3D computed tomography, complications, spasticity, chronic pain, cost effectiveness, fluoroscopy

Intrathecal drug delivery systems for the management of chronic non-cancer pain: protocol for a systematic review of economic evaluations

IntroductionIntrathecal drug delivery (ITDD) systems are an option for the management of patients with chronic non-cancer pain, cancer pain and spasticity. Concerns over their invasiveness and high initial costs have led National Health Service (NHS) England to decommission ITDD for patients with chronic non-cancer pain. However, the extent to which this decision is in line with existing economic evidence is unclear. To address this question, we will carry out a systematic review to identify and evaluate the existing evidence on the cost-effectiveness of ITDD for chronic non-cancer pain.Methods and analysisA high-sensitivity search strategy will be employed in Cochrane Library, MEDLINE, EMBASE, Web of Science, NHS EED, DARE and HTA. Database searches will be complemented by additional searching techniques. Screening of the results will be performed by 2 reviewers independently using predetermined inclusion and exclusion criteria. Full and partial economic evaluations will be included. Data extraction will be carried out using a form created for the purposes of this review. Quality assessment of all included studies will be performed using recommended checklists.Ethics and disseminationEthical approval is not required as primary data will not be collected. Findings will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration numberCRD42016035266.

Intrathecal management of complex regional pain syndrome: A case report and literature

Background and purposeComplex regional pain syndrome (CRPS) is a painful condition typically resulting from a traumatic event. Pain control in these patients is often difficult and requires a multimodal approach. Our objectives are to present a single intrathecal pain management regimen for CRPS and provide a literature review of intrathecal pain management options in CRPS. MethodsCase report from an academic pain management clinic. Case reportWe present the case of a 29-year-old female with a past medical history of multiple lumbar spine surgeries and lumbar post-laminectomy syndrome who presented to clinic with CRPS type II of the bilateral lower extremities. After failing conservative measures, she underwent placement of a successful intrathecal drug delivery system. ConclusionThe use of intrathecal medications is useful for pain control in CRPS patients. ImplicationsWe provide a framework for treatment of CRPS, which could be useful for practitioners dealing with this difficult and painful condition.

CE: Intrathecal Pumps for Managing Cancer Pain.

: It is estimated that more than 1.6 million new cases of cancer were diagnosed in the United States in 2014. Among patients with cancer, moderate to severe pain is prevalent and can be refractory, even with the use of systemic opioids, which may cause adverse effects that are difficult to manage at the doses required to control pain. When delivered intrathecally, however, opioids and adjuvant analgesics may provide greater pain relief at dramatically lower doses and with fewer adverse effects. Although the use of intrathecal drug delivery systems for cancer pain management has increased dramatically over the past several years and is expected to continue growing, patients with intrathecal pumps often report interactions with nurses unfamiliar with the technology. This article provides an overview of intrathecal pump therapy and explains how it prolongs duration of action and improves the efficacy of certain analgesics while reducing their adverse effects. The author discusses the costs involved, the patients most likely to derive benefit, the types of pumps currently used in the United States, the medications that can be delivered intrathecally, the potential risks and complications associated with intrathecal therapy, and the nursing care required by patients who use an intrathecal pump.

Sudden Intrathecal Drug Delivery Device Motor Stalls: A Case Series.

Intrathecal (IT) drug delivery systems (IDDSs) have been valuable in managing refractory chronic cancer and noncancer pain for more than 3 decades. These devices, time tested and overall reliable, have lately been noted at this institution to cease infusing unexpectedly. If not immediately recognized and rectified, this abrupt malfunction may lead to significant patient harm. A series of 13 patients from 1 academic center whose Medtronic SynchroMed II pumps malfunctioned from 2013 to 2015 is described. Data from the patient population with regard to variables that may increase the rate of IDDS malfunction are analyzed. The risk factors for IDDS malfunction, Medtronic-issued recalls, and current literature on IT device failure are reviewed. The total prevalence of device motor stall among the population of this institution is 9.03%. The incidence rate of IDDS failure is calculated at 0.04 device failures per patient per year. Increased length of time from implant was the only statistically significant (P = 0.00009) risk factor for device failure identified in this population. Dysfunction in the motor gear train was found after destructive analysis of several devices in this series. Higher rates of device failure are associated with the use of off-label IT drugs. However, device failure may still occur while infusing only approved medications. Implanted patients should be properly informed and educated to differentiate and recognize the critical error alarm of their device as well as the signs and symptoms of IT medication overdose and withdrawal.

Intra-Operative Computed Tomography Confirmation of Intrathecal Drug Delivery System Catheter

A 56 year old female presented with severe continued spasticity after revision of an implanted intrathecal drug delivery system for baclofen administration. The patient suffered a left temporal intracerebral hemorrhage with subsequent right spastic hemiplegia, upper extremity worse than lower. She underwent an initial intrathecal drug delivery system implant with catheter placement at T10. The medication did not affect spasticity of the right upper extremity. Therefore, the catheter position was revised to T4. Following the procedure, the patient was transferred to a skilled nursing facility for medical management and intrathecal baclofen dose titration. Despite titration of baclofen, the spasticity still persisted. Imaging studies, including radiograph, computed tomography and Magnetic Resonance Imaging demonstrated that the catheter tip was adherent to the dorsal membranes, consistent with placement in the subdural space, but possibly not the subarachnoid space. During the second revision of the catheter, intraoperative-computed tomography imaging of the patient’s spine was used to confirm placement prior to closure. This technique clearly demonstrated that the intrathecal catheter entered through the laminectomy at T7 and terminated at T4 in the intrathecal space as anticipated. Future use of this technique may demonstrate the improper placement of an intrathecal drug delivery system catheter. This would allow immediate revision of the catheter and prevent unnecessary returns to the operating suite.

An Overview of Pharmacologic Management of Chronic Pain.

Patients with chronic pain can be challenging to manage and historically providers have relied on opiates to treat pain. Recent studies have brought into question the safety and efficacy of chronic opiate therapy in the noncancer population. There is a vast amount of literature to support the use of nonsteroidal anti-inflammatory medications, antidepressants, anticonvulsants, topical agents, cannabinoids, and botulinum toxin either in conjunction with or in lieu of opioids. Intrathecal drug delivery systems can deliver some of these medications directly to their primary site of action while minimizing the side effects seen with systemic administration.

Intrathecal Analgesia for Chronic Refractory Pain: Current and Future Prospects.

The intrathecal drug-delivery system (IDDS) is one mode of infusing analgesic medications directly into the cerebrospinal fluid in close proximity to their site of action. This modality has been employed in patients with refractory pain either due to malignant or non-malignant causes for over 30 years. Unfortunately, and despite the number of years it has been in use, there is still a scarcity of rigorous evidence to guide its integration into clinical practice. Current best evidence is inconclusive as to the comparative effectiveness and harms of the IDDS relative to routine medical care of patients. There are far more systematic reviews than high-quality primary comparative studies of the IDDS vs. conventional pain treatment. Existing clinical practice recommendations are best viewed as expert opinion with competing interests. This article will review the existing literature for indications, contraindications, consensus statements, different technologies, and complications of the IDDS. Although approved analgesics for IDDS delivery are limited to morphine and ziconotide, many other analgesics, alone or in combination, are routinely used in this setting. This review will also focus on the pharmacology, clinical efficacy, and safety of intrathecal medications extensively used in clinical practice; including agents approved, unapproved, and under development.

Trialing and Maintenance Dosing Using a Low-Dose Intrathecal Opioid Method for Chronic Nonmalignant Pain: A Prospective 36-Month Study.

To evaluate low-dose intrathecal opioid trialing and maintenance with regard to analgesia and psychometric functional capacity. Prospective cohort of subjects offered, trialed and maintained using low-dose opioid therapy via an intrathecal drug delivery system. Analgesia, measured by visual analog scale and the Global Pain Scale, and function, measured by Multidimensional Pain Inventory and Global Pain Scale, are evaluated. Population analysis by age, gender, oral opioid dose, diagnosis, and pain type is reported. Fifty-eight subjects enrolled in the 36-month evaluation period with mean opioid intrathecal opioid dose less than 350 μg per day of morphine equivalent utilized. Primary nociceptive pain type were associated with lower intrathecal opioid doses and improved visual analog scale pain rating and improved pain severity and interference on the Multidimensional Pain Inventory. This study adds to the growing body of literature suggesting that low-dose intrathecal analgesia without oral opioid supplementation can be efficacious. It appears that this approach may achieve analgesia with lower doses in those with primary nociceptive pain type.

Persistent Spinal Headache After Removal of Intrathecal Drug Delivery System: A Case Report and Review of Literature

Introduction:To report and discuss the spinal headache following insertion and removal of intrathecal drug delivery system in patients with chronic pain disorders.Case Presentation:Intrathecal drug delivery system (IDDS) was initially used for the management of chronic malignant pain; it has since been used to manage pain from other nonmalignant conditions as well. Spinal headache is one of the complications during the trial, permanent placement and after removal of intrathecal drug delivery catheter systems. A 48-year-male patient with chronic pain disorder developed a refractory spinal headache after removing the intrathecal drug delivery system requiring a surgical intervention to resolve the problem.Conclusions:Conservative management is successful in the vast majority of patients with spinal headache. Interventional procedures are required in a small fraction of patients for symptomatic relief.

Successful Discontinuation of Systemic Opioids After Implantation of an Intrathecal Drug Delivery System.

An implantable drug delivery system (IDDS) provides an alternate route of opioid administration for patients with chronic pain. We collected data on systemic opioid use before and after IDDS implantation; patients who successfully discontinued systemic opioids; and physician support of discontinuation. This was a single-center, retrospective chart review of 99 consecutive patients who used IDDSs for at least six months. Data collection included pre/postimplant systemic opioid use and pain scores, and patient demographic and clinical characteristics. The study population averaged 67 years of age, was 68% women, and 77% were Medicare beneficiaries. Ninety-five percent of patients had low back pain, and 86% had limb pain. The majority (81%) had pain for >5 years. Failed treatments included epidural injections (74%), lumbar spine surgery (46%), spinal cord stimulation (14%), and facet joint injections (11%), with 84% also reporting significant systemic opioid side-effects. All patients taking long-acting opioids discontinued these within one month of implant. Total systemic opioid elimination was accomplished by 68% of patients at one month postimplant, 84% at one year, and 92% at five years. At one month postimplant, 60% of patients reported decreased pain (mean change: -4.07), and at one year, 64% did (mean change: -3.42). IDDS can provide significant and lasting pain relief and an alternate route of delivery compared with systemic opioids with their associated side-effects. We demonstrated that systemic opioid elimination could be accomplished after IDDS implantation in the majority of cases through appropriate patient selection, monitoring, and participation.

Managing intrathecal drug delivery (ITDD) in cancer patients.

Pain is a commonly reported symptom in cancer patients. Patients with cancer pain often fail conservative medical management or have significant side effects to systemic medications. The implantation of an intrathecal drug delivery (ITDD) system may be the most effective treatment option for these patients and can improve their quality of life. This article aims to discuss the choice of intrathecal medications for patients suffering from intractable cancer pain, the management of ITDD throughout a patient's disease course, and the management of complications related to the ITDD system and intrathecal medications.