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Guide Intrathecal Drug Therapy for Spasticity and Pain: Practical Patient Management

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The pump can be an external device or a fully implanted system with a reservoir that can be refilled percutaneously. There are two types of fully implantable pumps: Various infusion options are possible: The pump can be programmed for the patient to self-administer boluses.

Intrathecal drug delivery systems | BJA Education | Oxford Academic

The physician can set the bolus dose, the duration of infusion, the lock-out interval, and the maximum number of activations allowed per day; the patient activates the bolus facility. There is a suggestion that using a low-dose background infusion with a required bolusing regime may reduce the incidence of granuloma formation.

It certainly reduces the development of the tolerance and tachyphylaxis to bupivacaine and opioid infusions that occurs over time. The disadvantages are reduction in time between refills and the increase in use that inevitably shortens the life of the battery.

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The technology involved at the patient interface is relatively simple, but some degree of understanding and dexterity is still required. Each system has its own advantages, disadvantages, and limitations. Systems with external reservoirs and pumps have the major advantages of simplicity and cost. It is relatively easy and cheap to implant a catheter and start an infusion.

External reservoirs are easy to change and dose alterations are simple. The use of relatively high volumes for example, of dilute local anaesthetics, is possible. Physician administered boluses are possible. The problem is then in having trained professionals to manage the patient thereafter. Trained staff need to be available to deal with any problems and to refill and adjust the pump. Place of care may be limited to hospital or hospice depending on the availability of trained staff in the community. Negatives also include the bulkiness of the pump itself and the on-going risks of accidental disconnection and infection.

In the longer term, practically for any infusion intended to be running for longer than 3 months, a fully implanted system is a feasible economic option. Current evidence has led to several recommendations for both maximizing efficacy and minimizing potential toxicity of IT drugs: The aim of an ITDD system is to deliver the chosen drug to its receptor sites in the dorsal horn of the spinal cord in sufficient quantity to have a clinical effect.

Some basic principles are involved; knowledge of these determines where the tip of the catheter needs to be positioned and explains why the effects of slow IT infusions and boluses do not mimic the effect of spinal drugs given in relatively large volumes over a fraction of a second during the course of an anaesthetic. There is still some controversy regarding cerebrospinal fluid CSF fluid dynamics. Instead, it is clear that at a spinal level, CSF circulates or oscillates in a pulsatile fashion related to heart rate in a series of doughnut-shaped entities with areas of local turbulence around the boundaries of the canal and points of exit of nerve roots.

There is no overall flow, even for a drug injected into the ventricles.

Drug spread in the CSF depends on a variety of factors including buoyancy, streaming, injection rate, and enhanced diffusion. Diffusion itself is not particularly important as it takes 24 h for a drug to diffuse 1 cm. Slow continuous infusions from ITDD systems e.

What ITDD systems are available?

Experimental work using a pig model and methylene blue shows substantial dye at the level of infusion. Staining is only visible at the site of exit of the drug from the catheter. Even a bolus does not break beyond these boundaries, although there is some improvement in distribution within it. A high-volume 2—3 ml anaesthetic bolus administered over a second or two, with maybe a bit of barbotage, is distributed far more widely and the drugs easily break through the local CSF fluid circulation.

Drug factors physico-chemical properties and pharmacokinetics are, of course, important and for a big highly ionized molecule like ziconotide mean that it is eventually widely distributed throughout the neuraxis, whereas the small opioids are not.


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Lipid solubility largely determines how a drug is partitioned in grey matter, white matter, blood, and fat. Lipid-soluble drugs are likely to be cleared rapidly from the CSF to the fat of the epidural space and to plasma. More water-soluble drugs are likely to be distributed more widely, but penetrate the layers of the spinal cord less well. Some lipid-soluble drugs are cleared so fast that they have no clinical effect at a spinal level at all. It is clear that any spinal catheter needs to be sited at least at the dermatomal level of the pain for the infused drugs to have any chance of the drugs getting to the relevant receptor sites in the spinal cord.

It should also lie posteriorly within the spinal canal. It is worth noting that most catheters are multi-ported, but that infusions leave the catheter through only one of those ports. There are only two drugs licensed for use in ITDD systems for use in patients with chronic pain—morphine and ziconotide—but other opioids, local anaesthetics, and clonidine are commonly used, both alone and in combination.

It is mandatory that any drug used in the intrathecal space must be preservative free, not just because of the risk of neurotoxicity, but as there is the potential for some of the preservatives to react with CSF-proteins forming complexes that can cause catheter blockage. Unlike anaesthetic practice, local anaesthetics are not so frequently used for a variety of reasons—tachyphylaxis and the tingling and numb sensations, sometimes with incontinence and motor weakness—not great in the long term even for patients with progressive cancer-related pain.

Clonidine works well for neuropathic pain. Ziconotide is a relatively new drug still finding its place in the armamentarium, but it is effective for both nociceptive and neuropathic pain and for more generalized pain conditions. Any other drug is not in mainstream use but may have an application in certain clinical circumstances. Opioids work pre- and post-synaptically by depressing neurotransmitter release and hyperpolarizing neuronal membranes in the dorsal horn of the spinal cord. With time there is a functional uncoupling of the link, reflected clinically by the development of tolerance.

It is worth noting that ziconotide binds directly to the calcium channels with no development of tolerance with time. Serous opioid-related side-effects include opioid-induced hyperalgesia, hypotension, respiratory depression, and hypogonadotropic hypogonadism that can result in sexual dysfunction and osteoporosis. However, continuous simple opioid infusions remain the mainstay of chronic IT practice. It is a small hydrophilic molecule with a half-life in CSF of 80 min.

It has a relatively longer onset and duration of action than other opioids, but significant problems with tolerance, hyperalgesia, IT granulomas, and endocrine effects. A mg oral morphine equivalent is approximately converted to 1 mg IT.

It can be used in combination with local anaesthetics and clonidine. There are predictably fewer supra-spinal effects reported and more stable in combination with ziconotide than morphine. It can likewise be used in combination with local anaesthetics and clonidine. Case Studies in Neurological Pain. Modern Colposcopy Textbook and Atlas.

Intrathecal Drug Delivery

American Society for Colposcopy and Cervical Pathology. Ultimate Review for the Neurology Boards. Manual of Pediatric Neurology. Landmark Papers in Neurosurgery. The Hospital Neurology Book.

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Neuromuscular Case Studies E-Book. Chordomas and Chondrosarcomas of the Skull Base and Spine. Controversies in Neurosurgery II. The Textbook of Spinal Surgery. Fundamentals of Neurologic Disease. Congenital Anomalies of the Upper Extremity. Treatment of Hydrocephalus Computer Tomography. Disorders of the Neonatal Airway. Pituitary Tumors in Pregnancy. Atlas of Neurosurgical Techniques.


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  6. Textbook of Peripheral Neuropathy. Brain and Spine Surgery in the Elderly. Deja Review Neuroscience, Second Edition. Sleep Issues in Neuromuscular Disorders. Other suggestions to minimize the risk of granuloma formation include placing the catheter tip below the level of the conus when possible and using adjuvant non-opioid analgesics or ziconitide. This should include taking a complete history and physical on all patients receiving IT therapy at least every 6 months and monitoring for signs and symptoms of granuloma formation Figure 2.

    In conclusion, there are many challenges when taking over the care of a patient with an IT drug delivery system. With no clear standards to aid clinicians, it is best to re-evaluate the patient and tailor care to match available recommendations established by the recent Polyanalgesic Consensus Conference. It is strongly recommended that transfers of care involving a pump patient be planned in advance with all parties involved to optimize the overall treatment of the patient. When the patient and new managing physician engage in shared decision making within the framework of IT drug delivery guidelines, then a very rewarding and beneficial therapeutic relationship can be achieved.

    American Society of Regional Anesthesia and Pain Medicine Advancing the science and practice of regional anesthesiology and pain medicine to improve patient outcomes through research, education, and advocacy 3 Penn Center West, Suite Pittsburgh , PA About Calendar Patient information Corporate partners Donate.