Intrathecal Drug Delivery Research Articles

Intrathecal Drug Therapy in Chronic Pain Management

Chronic pain impacts the quality of multiple functional domains, including family life, workplace performance, social interactions, and sleep patterns. The management of chronic pain continues to pose many challenges to healthcare providers. Intrathecal drug delivery systems (IDDS) provide an effective therapy for patients suffering from chronic pain intractable to medical management. to identify best practices and provide guidance to clinicians to ensure safety and optimize intrathecal drug delivery for chronic intractable pain management. This is a review article, The search was performed in MEDLINE, Embase, Pubmed and CINAHL Plus in the same date range with the following mediacl terms. Intrathecal drug (IT) delivery has many benefits compared with oral or parenteral routes for pain control. First, it allows for the use of significantly lesser doses of opioids. Second, it bypasses the first pass effect and the blood brain barrier. Third, patients typically experience fewer adverse effects (AEs) due to the decreased total dose of opioid used. However, IT therapy may be associated with complications related to many factors, including those related to the IT pump itself (e.g., mechanical failure), pump pocket fills, issues surrounding preparation of the IT medication and programming of the pump for medication release, and complications following pump implantation surgery. Optimal use of this therapy depends on a thorough understanding of intrathecal physiology and anatomy as well appreciation of physicochemical properties of administered medications and the mode of IT delivery.

Narrative review of intrathecal drug delivery (IDD): indications, devices and potential complications.

The management of chronic refractory pain (non-neoplastic and cancer-related pain) remains a therapeutic challenge. The continuous intrathecal (IT) administration of drugs may play an important role in the possible management options. Intrathecal drug delivery devices (IDDDs) may be effective for patients with refractory chronic pain. Therefore, they may be adopted for non-oncologic pain in patients with compression fractures, spondylolisthesis, spondylosis, back surgery failure syndrome and spinal stenosis. Oncologic patients can benefit from these treatments in a variable way according to tumor characteristics, prognosis, periprocedural imaging and risk of disease progression. In this review, we describe the most commonly used drugs (opioids and non-opioids), their pharmacokinetic and pharmacodynamic features and indications of use. The most used drugs are morphine, hydromorphone, fentanyl, methadone, bupivacaine, clonidine, and ketamine. Patient evaluation before the device implantation should be based on clinical examination, medical records assessment and psychometric evaluation. The infusion pumps available on the market are both non-programmable (with continuous IT deliver of drugs) and programmable (with variable deliver of drugs according to their flow rate). Moreover, we describe the procedure of implantation and the potential complications of IT drug delivery (such as bleeding, infection, loss of cerebrospinal fluid, wound seroma, loss of catheter pump propellant).

A Retrospective Analysis of Intrathecal Catheter Tip Position in Plain Radiography: How Much Do We Agree?

To assess interrater and intrarater reliability of postoperative plain radiographs, which are routinely performed to confirm the correct placement of the catheter tip after intrathecal drug delivery systems (IDDS) implantation. This was a retrospective analysis of plain radiographs obtained from patients implanted with intrathecal catheters and morphine pumps. Each plain radiograph was assessed independently by three raters with varying expertise, at three different time points, to confirm the position of the intrathecal catheter tip. Krippendorff?s alpha coefficient was used to calculate both the interrater and intrarater reliability. There was a high level of agreement among the three raters and the three reviews of each rater separately when assessing the location of intrathecal catheter tips in plain radiographs from 126 patients. This was evidenced by the Krippendorff?s alpha value being > 0.99 in all cases, which was greater than the cutoff threshold value of 0.8. The interrater and intrarater reliability of plain radiographs for determination of catheter tip position after IDDS implantation was high. The experience and expertise of the raters did not significantly affect the assessments.

Conundrum of chronic pelvic pain and a pelvic journey of unparalleled grit: The good, the bad, and the ugly

Conundrum of chronic pelvic pain and a pelvic journey of unparalleled grit: The good, the bad, and the ugly

Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys.

A detailed understanding of the CSF dynamics is needed for design and optimization of intrathecal drug delivery devices, drugs, and protocols. Preclinical research using large-animal models is important to help define drug pharmacokinetics-pharmacodynamics and safety. In this study, we investigated the impact of catheter implantation in the sub-dural space on CSF flow dynamics in Cynomolgus monkeys. Magnetic resonance imaging (MRI) was performed before and after catheter implantation to quantify the differences based on catheter placement location in the cervical compared to the lumbar spine. Several geometric and hydrodynamic parameters were calculated based on the 3D segmentation and flow analysis. Hagen-Poiseuille equation was used to investigate the impact of catheter implantation on flow reduction and hydraulic resistance. A linear mixed-effects model was used in this study to investigate if there was a statistically significant difference between cervical and lumbar implantation, or between two MRI time points. Results showed that geometric parameters did not change statistically across MRI measurement time points and did not depend on catheter location. However, catheter insertion did have a significant impact on the hydrodynamic parameters and the effect was greater with cervical implantation compared to lumbar implantation. CSF flow rate decreased up to 55% with the catheter located in the cervical region. The maximum flow rate reduction in the lumbar implantation group was 21%. Overall, lumbar catheter implantation disrupted CSF dynamics to a lesser degree than cervical catheter implantation and this effect remained up to two weeks post-catheter implantation in Cynomolgus monkeys.

Response to Letter to the Editor regarding: Managing Intrathecal Drug Delivery Devices in a Global Pandemic

Response to Letter to the Editor regarding: Managing Intrathecal Drug Delivery Devices in a Global Pandemic

Response to: Managing Intrathecal Drug Delivery Devices in a Global Pandemic

Response to: Managing Intrathecal Drug Delivery Devices in a Global Pandemic

Intrathecal Drug Delivery System: A Pain Management Option for Refractory Cancer-Related Pain.

Cancer-related pain is progressive and therefore requires a stepwise approach to management, such as the World Health Organization's Pain Ladder. This approach calls for increasingly strong pain medications in addition to interventional options for patients with medication-refractory pain or intolerable medication side effects. Here, we discuss a case involving cancer-related pain which ultimately required intrathecal drug delivery system placement for optimal pain management.

Intrathecal Drug Delivery for Chronic Pain Syndromes: A Review of Considerations in Practice Management

Background Chronic pain syndromes are poorly understood and challenging to treat. However, intrathecal drug delivery systems (IDDS) have been shown to have good efficacy in treating various pain subtypes and patient populations. The success of IDDS interventions is largely dependent on consideration of and adherence to varying practice patterns. Objectives We aimed to review and report on the evidence basis for various considerations in IDDS practice management including: (1) patient selection and periprocedural criteria, (2) efficacy of IDDS for various conditions, (3) intrathecal medications, (4) drug delivery systems, (5) trial and implantation, (6) complications and adverse events, and (7) chronic follow-up. Study design We conducted an evidence-based narrative review. Methods PubMed, Medline, Cochrane Library, prior systematic reviews, and reference lists were screened by 2 separate authors for all randomized trials, meta-analyses, and observational studies relevant to each of the aforementioned management principles and were considered for study inclusion. Results All high-level evidence studies that explored the various facets for IDDS practice management were included for review. Limitations Despite existing evidence basis for practice considerations, current practice patterns are highly practitioner dependent. More and continued high-level evidence is necessary to support, affirm, and dictate principles in practice considerations. Conclusions Incorporation of the principles found in this evidence-based narrative, which is comprised of the highest level of evidence supportive of various facets of IDDS practice management, is essential to optimize outcomes, treatment efficacy, and safety profiles.

Peripheral Nerve Stimulation of the Lateral Femoral Cutaneous and Superior Gluteal Nerves for Treating Proximal Neuropathy Hip Pain

Background: Chronic postoperative hip pain is estimated to occur in 10% to 35% of patients undergoing total hip replacement. Proximal peripheral neuropathic pain of the lateral femoral cutaneous and superior gluteal nerves has proven to be a difficult disorder to treat. Opioids are often ineffective in the treatment of neuropathic pain. Interventional methods such as peripheral nerve stimulation are minimally invasive options capable of relieving neuropathic pain. Stimulators powered by an implantable pulse generator (IPG), however, may not be suitable for peripheral nerve stimulation because of difficulty finding an appropriate pocket site. The introduction of wireless peripheral nerve stimulation has improved the ability to offer this modality. Case Presentation: We present a case of proximal peripheral neuropathic pain of the lateral femoral cutaneous and superior gluteal nerves that failed all other treatment modalities including spinal cord stimulation and intrathecal drug delivery. Two quadripolar, tined, wireless electrode arrays were positioned over the lateral femoral cutaneous and superior gluteal nerves. A stimulation scheme with a pulse rate of 1.5 kHz and pulse width of 30 μs at 2.0 mA was tested and found effective. Conclusion: This patient had proximal neuropathic hip pain and failed a variety of chronic pain treatment options, including conventional IPG-based spinal cord stimulation and an intrathecal drug delivery system. She was successfully treated with a wireless peripheral nerve stimulation system. Key words: Hip pain, lateral femoral cutaneous nerve, peripheral nerve stimulator, peripheral neuropathy, superior gluteal nerve

Blame it on the Pump

Intrathecal drug delivery a method of directly administering opioid and spasmolytic medication to the site of action, the spinal cord. Efficacy and safety of this delivery system is well documented in cancer pain, spasticity as well as non-malignant pain. However, there are a number of recognised potential complications with this therapy. One of the most serious of which is the formation of a granuloma occurring at the intrathecal catheter tip, which appears to be related to the concentration and drug type being delivered. Evidence has indicated that delivery of high dose morphine can lead to the formation of these granulomas. Occurring in less than 3% of all patients with an intrathecal catheter, granulomas can present as an inflammatory mass on imaging with some resulting in compression of the spinal cord. Patients may present with a host of neurological symptoms dependent on the location of cord compression caused by the granuloma, including neurological deficits, myelopathy and radiculopathy.

The Unmet Need for Intrathecal Drug Delivery Pumps for the Treatment of Cancer Pain in England: An Assessment of the Hospital Episode Statistics Database

Intrathecal drug delivery (ITDD) devices have been shown to be a clinically effective and cost-effective option for the management of cancer pain and recommended for use in England. The aim of this study is to assess the impact of the 2015 NHS England Clinical Commissioning Policy on the uptake of ITDD pumps for the management of cancer pain or if there is an ongoing unmet need for this intervention in England. Hospital Episode Statistics (HES) were obtained for all patients undergoing ITDD for the management of cancer pain between 2014 and January 2020. In addition, HES were utilized to estimate the number of patients with cancer potentially eligible for ITDD pump during the same period. The number of patients with cancer and those potentially suitable to receive an ITDD for the management of cancer pain have increased year on year since 2014. This increase has not been matched by an uptake in the provision of ITDD. Conservative estimates suggest that at least 8000 people with cancer pain would be eligible for ITDD; 458 patients received an intervention for pain management between April 2018 and March 2019 and only 30 ITDD pumps were implanted in that same period. We observed a substantial gap between the need and provision of ITDD for patients with refractory cancer pain in England despite the recommendation for the use of ITDD for this patient population. In addition, we present suggestions for improvement of access to and provision of ITDD in England.

Initiation of Intrathecal Drug Delivery Dramatically Reduces Systemic Opioid Use in Patients With Advanced Cancer

Pain is common in cancer, affecting more than 70% of patients with advanced disease. Intrathecal drug delivery systems (IDDS) are a well-established treatment for patients with refractory cancer pain, improving pain control and reducing associated side effects. To date, details of systemic opioid use before and after IDDS implant have not been reported. We conducted a retrospective review of patients at Huntsman Cancer Institute-University of Utah treated with IDDS for cancer pain from May 2014 to May 2018. Oral, transdermal, and parenteral opioid use before IDDS implant was compared to use 30 days postoperatively. A total of 173 patients were included, 93% with stage IV disease. The pre-implant median daily oral morphine equivalent (OME) was 240 mg (interquartile range 130-390, range 0-2616 mg). OME doses >200 mg/day were required by 57% of patients, and >500 mg OME by 19% of patients. The post-implant median OME was 0 mg (interquartile range 0-0, range 0-480 mg) and 82.6% of patients discontinued systemic opioids completely. 11.0% of patients used <100 mg OME, and only 1.7% of patients used >200 mg OME. Mean OME decreased by 94% following IDDS implant (p < 0.0001) and all patients who continued to use systemic opioids required a lower OME compared to pre-implant. In the largest cohort of patients with advanced cancer and refractory pain treated with IDDS, implantation was associated with a dramatic reduction in systemic opioid use 30 days postoperatively, with a large majority of patients discontinuing systemic opioids. Those patients that continued systemic opioids utilized significantly lower doses as compared to their pre-implant dose.

Systemic Opioid Reduction and Discontinuation Following Implantation of Intrathecal Drug-Delivery Systems for Chronic Pain: A Retrospective Cohort Analysis

ObjectiveThe study evaluated systemic opioid utilization before and after initiation of intrathecal drug therapy in patients with chronic, noncancer pain, as well as the effect of opioid elimination on payer costs.MethodsThis was a retrospective cohort analysis of administrative claims data (2011‐2016), evaluating patients using systemic opioids for chronic, noncancer pain, newly implanted with an intrathecal drug‐delivery system. Patients were excluded for spasticity, cancer, and device explant. The primary outcome was reduction or discontinuation of systemic morphine milligram equivalents during a 395‐day follow‐up period. The secondary outcome was total commercial insurer payments.ResultsOf 9223 total patients, 631 met selection criteria. From baseline to 395‐day follow‐up, average daily morphine milligram equivalents decreased in 81.5% of patients, and 43.3% discontinued systemic opioid therapy entirely. Among patients who continued systemic opioids, average daily morphine milligram equivalents decreased in 74.9% of patients. Logistic regression found that morphine milligram equivalents of <50 mg/day prior to initiation of intrathecal drug delivery was associated with two times the odds of discontinuation vs. ≥90 mg/day (odds ratio = 2.08, 95% confidence interval 1.42‐3.02, p = 0.001). Mean annual payer costs were reduced 29% for patients who discontinued vs. continued systemic opioids (−$11,115 per patient).ConclusionsA meaningful proportion of patients discontinue or decrease systemic opioid use following initiation of intrathecal drug delivery. Standard of care should include opioid dose tapering prior to intrathecal drug delivery to maximize the probability of systemic opioid discontinuation.

A Comparison of Refill Procedures and Patient Outcomes Following Ultrasound-Guided and Template-Guided Intrathecal Drug Delivery Systems With Recessed Ports

Intrathecal drug delivery systems (IDDS) are refilled using templates and palpation. The 2017 Polyanalgesic Consensus Conference recommends ultrasound only when reservoir ports are difficult to identify. The purpose of this study was to compare procedural outcomes and patient's preference for refill method of IDDS. The study was approved by the Rush University IRB. Participants were randomized to have their IDDS with ultrasound or template using a 2:1 allocation. The time to reservoir port access, number of needle maneuvers/punctures, pain (NRS 0-10), complications, patient satisfaction, and patient refill modality preference, were recorded. A total of 107 patients underwent 192 refills. There were 67 template-guided refills and 125 ultrasound-guided refills. No procedural pain (NRS = 0) was reported in 84% of the ultrasound-guided refills compared with 67% of the template-guided procedures, difference - 17% (95% difference - 3% to -31%, p = 0.01). When adjusted for age, gender, procedure duration, needle sticks, needle maneuvers and refills in the same patient, the odds ratio for a pain-free procedure with ultrasound-guidance was 3.1 (95% CI 1.3 to 7.2, p = 0.01). There was no difference between the groups in needle punctures (p = 0.87) or redirections (p = 0.34). Following 35/67 (52%) template-guided procedures, patients stated they preferred the ultrasound-guided but following only 12/125 (10%) of ultrasound-guided procedures, patients stated they preferred template-guidance (p < 0.001). Patients preferred ultrasound even though it lengthened the duration of refills compared to template-guided procedures. Fewer patients experienced procedural pain with ultrasound compared with template-guided refills. No safety issues were observed in either group.

A Case Report of Reticular Telangiectatic Erythema Following Intrathecal Drug Delivery System Reservoir Replacement

A Case Report of Reticular Telangiectatic Erythema Following Intrathecal Drug Delivery System Reservoir Replacement

Evaluation of Fixed Intrathecal Bupivacaine Infusion Doses in the Oncologic Population

Intrathecal drug delivery systems (IDDS) are an important method of pain control for patients with refractory oncologic pain. Local anesthetics such as bupivacaine have been infused either alone or with opioids. While effective, bupivacaine can cause adverse effects such as numbness, weakness, and urinary retention. This study looks to establish a safe and efficacious fixed bupivacaine dosing algorithm in intrathecal pumps for cancer patients. A bupivacaine dosing algorithm was developed using data from 120 previous patients who underwent IDDS placement at Memorial Sloan Kettering Cancer Center. The outcomes were then evaluated for 43 subsequent patients who were treated with bupivacaine IDDS according to our aforementioned algorithm. Our data show that in patients treated with our bupivacaine guideline, visual analog pain scale scores decreased by 59% and oral morphine equivalence decreased by 70% from the period between IDDS implantation until discharge from the MSKCC hospital. However, 16.3% of our patients had bupivacaine-related side effects. For oncological patients, our data and experience support the initiation of intrathecal bupivacaine at the following doses: 5 mg/day for catheter tips in the cervical spine, 8 mg/day for catheter tips at T1-4, and 10 mg/day for catheter tips at T5-8. Given the higher likelihood of adverse effects in catheters at T9-12 and the lumbar spine, we start at 8 mg/day with close follow-up of the patient. Initiating these doses allow our patients to safely reach adequate analgesia faster, with a shorter hospitalization and quicker return to anti-cancer therapy.

Accuracy of Template Versus Ultrasound Identification of the Reservoir Access Port of Intrathecal Drug Delivery System

Precise localization of the center of the reservoir access port (RAP) of intrathecal pump is a crucial step to ensure a safe refill procedure. In difficult refill cases, ultrasound guidance has been reported useful. Being more expensive and time-consuming, the purpose of the study was therefore to identify situations in which sonographic localization is more accurate than the template method, in order to restrict its use to these defined conditions. The RAP was localized using the template provided by the manufacturer and by ultrasound guidance. The distance between the two points was measured. A distance superior to 3.5 mm, corresponding to the radius of the silicone septum of the RAP, was considered a clinically significant deviation. During the study period, 22 patients underwent a total of 81 refill procedures. No significant correlation was found between the distance between the two points and age, height, weight, body mass index (BMI) or abdominal perimeter. The correlation was significant between distance and pump's depth. According to the ROC curve, the sensitivity of ultrasound identification of the RAP was 69.2% and the specificity 83.3% when the pump was implanted at a depth of 10 mm. Our results are comparable to these published in the literature, pointing the usefulness of ultrasound for refill of deeply implanted pumps. Our study provides an additional element by specifying the depth from which the ultrasound seems to be superior to template. Poor accuracy in RAP identification of intrathecal pump can lead to life-threatening complications. The results of our study suggest that the localization of recessed-RAP can be improved by ultrasound in cases of pump implanted deeper than 10 mm. For more superficially implanted devices, the template method seems to be as accurate as ultrasound.

Awareness about Intrathecal Drug Administration among Dental students

Intrathecal administration includes the immediate infusion of the medication in Cerebro Spinal Fluid(CSF) internal to the intrathecal space of the spinal column. The intrathecal course permits direct medication organization to the CSF by evading the blood-cerebrum hindrance. It permits conveyance of small medication dosages, and the event of adverse effects are decreased compared with systemic courses of medication administration. This survey was performed for assessing the awareness about intrathecal drug administration among dental students. A cross-sectional study was done with a self-administered questionnaire with ten questions circulated among 100 dental students. The questionnaire assessed the awareness about intrathecal drug delivery in medical applications, their medicinal uses, drugs administered, mechanism of action and side effects. The responses were recorded and analysed.17% of the respondents were aware of medical uses of intrathecal drug delivery, 13% were aware of the drugs used in intrathecal drug delivery .10 % were aware of the mechanism of action of intrathecal drug delivery .7% were aware of side effects of intrathecal drug delivery. The awareness about intrathecal drug administration among dental students is not adequate. Increased awareness programs and continuing dental education programs in intrathecal drug delivery should be initiated to improve the awareness levels.

20th Annual FAER-Helrich Research Lecture

Anesthesiology 2020| September 2020 20th Annual FAER-Helrich Research Lecture Ruth Waterman, MD, MS Ruth Waterman, MD, MS Search for other works by this author on: This Site PubMed Google Scholar ASA Monitor September 2020, Vol. 84, 31. https://doi.org/10.1097/01.ASM.0000717008.40522.6b Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Search Site Citation Ruth Waterman; 20th Annual FAER-Helrich Research Lecture. ASA Monitor 2020; 84:31 doi: https://doi.org/10.1097/01.ASM.0000717008.40522.6b Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search nav search search input Search input auto suggest search filter All ContentAll PublicationsASA Monitor Search Advanced Search The 20th Annual FAER-Helrich Research Lecture will be presented on October 3 by Tony L. Yaksh, PhD, MS a member of the Department of Anesthesiology at the University of California, San Diego. Dr. Yaksh's formidable career has focused on the mechanisms of pain, and he has made many observations and discoveries that have advanced the field. Tony is well-known for being a collaborative and generous colleague who has promoted the careers of many. Prior to arriving at UC San Diego in 1988, Dr. Yaksh served in the U.S. Army, then spent time at the University of Wisconsin, University College London, and Mayo Clinic Rochester investigating mechanisms of opiates and non-opiates in the modification of central nervous system pain processing, studying basic physiology of unmyelinated fibers of the nervous system, and investigating neurotransmitter release. He developed an intrathecal drug delivery... © 2020 American Society of Anesthesiologists (ASA), All Rights Reserved.2020 You do not currently have access to this content.