Intrathecal Drug Delivery (ITDD) systems for cancer pain

Bhatia, Gaurav; Lau, Mary E; Gulur, Padma

doi:10.12688/f1000research.2-96.v1

Cited by 53 publications

(55 citation statements)

References 9 publications

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“…The initial IT morphine dose was calculated from the baseline opioid use with an oral–IT morphine conversion ratio of 300:1. [11] The initial infusion was started at a flow rate of 0.1 mL/h without PCIA dose for safety reasons. IT morphine titration was conducted 1 day after the procedure.…”

Section: Methodsmentioning

confidence: 99%

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

Zheng

Yang

et al. 2017

Medicine

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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.

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Section: Methodsmentioning

confidence: 99%

“…Opioid use was calculated by morphine oral equivalent dose. [11] Systemic opioid use consisted of controlled-release opioid use (basal dose) and immediate-release as-needed opioid use (breakthrough dose). IT opioid use included continuous infusion morphine use (basal dose) and PCIA morphine use (PCIA dose).…”

Section: Methodsmentioning

confidence: 99%

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

Zheng

Yang

et al. 2017

Medicine

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“…This use of high concentrations in human pumps has led to local toxicity. For opiates, the manifestation of this toxicity is the intrathecal granuloma [37, 116, 461-463]. Our group showed that the primary determinant for intrathecal opiate granulomas is the local concentration to which the tissue adjacent to the catheter tip is exposed [49, 51, 52].…”

Section: Current Spinal Agentsmentioning

confidence: 99%

Current and Future Issues in the Development of Spinal Agents for the Management of Pain

Yaksh

Fisher²,

Hockman³

et al. 2017

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Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. The review covers i) the major classes of spinal agents currently employed as intrathecal analgesics (opioid agonists, alpha 2 agonists; sodium channel blockers; calcium channel blockers; NMDA blockers; GABA A/B agonists; COX inhibitors; ii) ongoing developments in the pharmacology of spinal therapeutics focusing on less studied agents/targets (cholinesterase inhibition; Adenosine agonists; iii) novel intrathecal targeting methodologies including gene-based approaches (viral vectors, plasmids, interfering RNAs); antisense, and toxins (botulinum toxins; resniferatoxin, substance P Saporin); and iv) issues relevant to intrathecal drug delivery (neuraxial drug distribution), infusate delivery profile, drug dosing, formulation and principals involved in the preclinical evaluation of intrathecal drug safety.

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“…Intrathecal drug therapy is often effective for patients with chronic and cancer pain. By delivering the drugs via an intrathecal route, the risk of side effects of analgesics may be significantly decreased due to the substantially smaller doses required when compared to drugs given systemically . However, there is a risk of inadvertently administering too large doses intrathecally.…”

Section: Anesthetic Agents and Pain Medicationsmentioning

confidence: 99%

Inadvertent intrathecal injections and best practice management

Liu

Tariq

Liu

et al. 2016

Acta Anaesthesiol Scand

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The intrathecal space has become an important anatomic site for medical intervention not only in anesthesia practice, but also in many other medical specialties. Undesired/inadvertent intrathecal injections (UII) are generally rare. There is tremendous variation in reported inadvertent administrations via an intrathecal route in the literature, mainly as individual cases and very small case-series reports. This review aims to identify potential sources of UII, its clinical presentations, and appropriate management. The inadvertent injectants are classified as anesthetic agents and pain medicines, chemotherapeutics, radiological contrast agents, antibiotics and corticosteroids, and miscellaneous chemical agents such as tranexamic acid. The clinical effects of UII are dependent upon inadvertent injectant(s) and dose being administered intrathecally, and can range from no adverse effect to profound neurological consequences and/or death. Prompt cerebrospinal fluid (CSF) lavage and cardiopulmonary support seem to be the mainstay of treatment. If serious consequences are anticipated, CSF lavage could be lifesaving. This review additionally provides some options for comprehensive management and preventing strategies.

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Intrathecal Drug Delivery (ITDD) systems for cancer pain

Cited by 53 publications

References 9 publications

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

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

Current and Future Issues in the Development of Spinal Agents for the Management of Pain

Inadvertent intrathecal injections and best practice management

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