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InFocus: Troubleshooting Intrathecal Drug Delivery Systems

Roberts, James R. MD

doi: 10.1097/01.EEM.0000508285.06009.26
InFocus

Dr. Robertsis a professor of emergency medicine and toxicology at the Drexel University College of Medicine in Philadelphia. Read the Procedural Pause, a blog by Dr. Roberts and his daughter, Martha Roberts, ACNP, CEN, athttp://emn.online/ProceduralPauseEMN, and read his past columns athttp://emn.online/InFocusEMN.

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Emergency clinicians are charged with evaluating and tackling the basics of almost any medical problem. Hardly a week goes by that even a seasoned veteran does not come across an issue or problem that he has never seen. One such potential enigma is the patient with possible problems from an intrathecal (IT) drug pump. These devices are not placed by emergency physicians, they are not programmed or filled with medication in the ED, and usually only specialists deal with them. That means when a clinical problem occurs, the emergency clinician is often rightly befuddled.

A physician familiar with these devices is not likely available in many smaller hospitals. The first task when a patient with an IT pump presents to the ED with a number of potential issues is to decide whether his complaints are actually related to a malfunction of the pump. That mandate may be easier said than done.

Most pain can be handled by oral analgesics, but the daily opioid dose for patients with chronic pain, such as those with cancer, can escalate to the point where intolerable side effects occur or the medication is no longer effective. Intrathecal drug delivery systems (IDDS) were introduced in the early 1990s as a method for controlling chronic pain and for treating neurologic-related spasticity after more traditional treatments were ineffective. An IDDS is a highly complex system essentially composed of a subcutaneous pump that stores drugs in a refillable reservoir and delivers them into the intrathecal/ subarachnoid space via a catheter.

Medication is delivered as a bolus or as a constant infusion. Some devices use an epidural terminating catheter, but most catheters are placed into the subarachnoid space at the level of the spinal cord where a specific effect is targeted. Opioids delivered intrathecally suppress substance P release by C fibers and modulate afferent information at the level of the spinal cord through a variety of complex mechanisms.

The goal of IT pain medication is to relieve pain effectively with minimal complications and decrease side effects of high doses of systemic opioids. Calculating the correct opioid or other medication dose to be delivered by the IDDS is outside the realm of emergency medicine, but only a small fraction of the required systemic dose is effective at the spinal cord level. Approximately one percent of the total daily morphine systemic dose, for example, is a reasonable starting dose for pump delivery into the intrathecal space. Spinal doses of morphine are reduced by a factor of 10-300 compared with daily oral doses. Often a temporary infusion is used prior to permanent device implantation to assess efficacy or the best drug dose.

Fixed rate and programmable bolus dose pumps are available. The drug-infusing pump is most commonly implanted subcutaneously in the lower abdominal wall, connected to a catheter that is advanced into the subarachnoid space at the desired level. Some catheters terminate at the epidural space, although most are placed in the intrathecal (subarachnoid) space. Patients with a relatively short life expectancy are treated with an external pump. The infusion device is implanted subcutaneously for the patient with a chronic condition.

Research strongly suggests a significant reduction in cancer pain with intrathecal pumps, but the actual effect of these devices has not been rigorously analyzed. Nonetheless, they are used more and more frequently, but problems can occur, as with any mechanical device.

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Intrathecal Drug Administration in Chronic Pain Syndromes

Ver Donck A, Vranken JH, et al.

Pain Pract

2014;14(5):461

The authors of this overview of intrathecal drug administration for patients with chronic pain note that IT therapy is not only used for chronic pain from cancer, but for a variety of benign pain conditions, failed back surgery, peripheral neuropathy, chemotherapy, and severe neurologic spasticity. Patient selection criteria for the use of an IT pump are outlined in the table. Intrathecal drug administration is the last step for patients with a variety of poorly controlled conditions. Interestingly, untreated drug addiction is an absolute contraindication to this form of therapy.

Choice of Agent: A number of medications have been used for neuraxial infusions. Morphine or the local anesthetic bupivacaine were used initially to target receptors in the dorsal horn of the spinal cord. Currently, first-line IT therapy uses morphine, hydromorphone, ziconotide, or fentanyl. A combination of medications is often used. Interestingly, clonidine and baclofen are also used for intrathecal therapy. Many patients benefit from intrathecal pumps, with an improved level of analgesia and decreased systemic effects such fatigue, alterations in level of consciousness, pruritus, and nausea.

Intrathecal Opioids: Opioids are placed in the intrathecal space under the premise that the agent gets immediate access to spinal pain pathways without producing significant systemic effects. Mechanisms of action include the inhibition of the release of substance P and interference with calcium channels, as well as activation of opioid receptors. Drug choice varies considerably and is institution specific, but morphine is often the opioid of first choice for IT administration for chronic pain. Fentanyl and derivatives such as sufentanyl are also used. Clonidine, an alpha 2 receptor agonist, is also used for pain control in the intrathecal space and can be combined with morphine. Other medications used for intrathecal therapy include baclofen, midazolam, bupivacaine, and ziconotide. Ziconotide is a calcium channel blocker for IT use that appears effective for patients with chronic benign or cancer pain syndromes. But many patients experience adverse side effects from IT ziconotide, such as nausea, dizziness, balance disorders, confusion, and urinary retention.

A number of retrospective reviews and prospective studies have termed IT therapy moderately effective and safe in controlling chronic pain syndromes not responsive to systemic analgesics. The clinical success rate is around 70-80 percent. Quality of life also appears to be improved in many individuals. A 2005 Cochrane review concluded that IT opioid therapy is often effective for treating cancer pain that has not been adequately controlled by systemic opioids.

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Side Effects and Complications of IT Drug Therapy: An unusual side effect of intrathecal therapy is the development of an intrathecal mass at the end of the infusion catheter that can cause spinal cord compression or cauda equine syndrome. These masses are related to the use of opioids and other drugs. Analysis demonstrates noninfectious inflammation and granuloma formation, with fibrosis or necrosis.

A particularly challenging scenario for the emergency clinician is the sudden discontinuation of IT drug administration, either from the pump running out of the drug, pump malfunction, or catheter displacement or fracture. This scenario often results in withdrawal syndromes, many of which can be severe or even life-threatening. Withdrawal is a particularly difficult issue to evaluate and treat in the ED.

Comment: The specifics of IT catheter placement, pump maintenance, and choice of medications is beyond the clinical expertise of the emergency clinician. Patients with complications often find their way to the local ED, however, because the specialist is often unavailable during off hours or complications are significant.

Complications Following Catheter Placement: Catheter insertion can be associated with bleeding and infections, but local bleeding is usually not an issue after the first three or four days. When drugs are first administered, gradual spread of an opioid in the cerebral spinal fluid can cause respiratory depression, often delayed 12-24 hours after injection. Overdose is rarely encountered during treatment of cancer pain in patients who have had prior opioid therapy.

Spinal anesthesia can result when local anesthetics are used, causing hypotension, motor weakness, paralysis, and loss of sensation. Meningitis and epidural abscess formation are significant complications, but they are unusual. Catheter migration or blockage and pump malfunction are also rare, but can result in the cessation of IT drug delivery. As mentioned, inflammatory masses — large granulomas — at the intrathecal catheter tip may develop in a minority of patients. These masses can become space-occupying lesions, especially in the thoracic area, that can cause devastating neurological consequences. They are best evaluated by MRI.

Approach to IT Pump Problems in the ED: It is prudent to ask a patient who comes to the ED with a condition that may be related to an IT pump if he has an identification card for it. This describes who placed the pump, how to contact them, and what medication is in the pump. Unfortunately, this is often unavailable. Perhaps counterintuitive, many conditions or symptoms that arise in patients on intrathecal pumps are not related to the pump itself. These devices are only placed in patients who have multiple medical problems. What seems like an overdose of medication is rarely caused by pump malfunction, for example. It may have been inadvertent misplacement of medications outside the loading port if the pump was recently filled. This medication enters the subcutaneous tissue — a so-called pocket shot — and can be rapidly absorbed.

Some patients will attempt to withdraw medications from their pump to inject for drug abuse. Others with chronic pain may also abuse oral or street medications that can simulate a pump-related overdose. More commonly, however, patients will present with withdrawal because of an empty pump, a malfunction of the pump, or a break in the catheter. Withdrawal is potentially serious and tricky to evaluate and ameliorate in the ED, and it cannot be handled alone by the emergency clinician.

Those who receive opioids, baclofen, or clonidine are most likely to exhibit severe withdrawal symptoms. Clonidine withdrawal can cause rebound hypertension and severe cardiovascular dysfunction, as well as panic attacks and psychotic behavior. Patients on pump-delivered baclofen will also experience significant withdrawal, accompanied by seizures and severe cardiovascular symptoms. Opiate withdrawal is similar to withdrawal from systemic opiate use.

One might intuit that simply giving parenteral or oral replacement of the drug used in the intrathecal pump would combat withdrawal, but importantly, this is usually not the case. I could not find a reasonable explanation for why; it must be related to direct spinal use of these medications. It requires significant amounts of oral or parenteral drug to reach the area of the spinal cord where the withdrawal symptoms originate. Exactly why spinal cord-initiated withdrawal is so difficult to treat and does not respond to standard therapy is difficult to understand. Attempting to treat opioid, baclofen, or clonidine withdrawal with those medications given systemically is usually not effective. Patients in withdrawal from these medications should be carefully evaluated with the help of a consultant, and it would be imprudent to believe that one could handle withdrawal as an outpatient by merely providing replacement oral medication. Even very large systemic replacement doses may not quell withdrawal.

Withdrawal patients should almost always be admitted to the hospital under the care of a specialist. Not well studied is the suggested use of intravenous propofol to combat severe withdrawal from baclofen. Patients may require enough propofol to need intubation, and intensive monitoring is required. Systemic opioid replacement can be massive enough to cause significant opioid toxicity while only partially ameliorating withdrawal symptoms.

Bleeding complications and infectious complications are rare once the pump and catheter have been in place for a number of days. If a lumbar puncture is required, proceed cautiously and only after the position of the catheter has been confirmed by an x-ray. It makes more sense to have a specialist withdraw cerebral spinal fluid directly from the side port of the pump, which has direct access to the spinal canal. Withdrawal treatment can also be facilitated by infusion of drugs through this side port, rather than trying to overcome withdrawal by systemic medications.

Patients with IT pumps may require anticoagulation or thrombolytics. It is generally safe to use anticoagulants and thrombolytics in patients who have had the pump in place for five to seven days, and no increased side effects have been noted with the delayed use of anticoagulation. Certainly, if the pump has been in place for many weeks or months, anticoagulants or thrombolytics can be given with only general precautions.

It may be necessary to obtain an MRI to evaluate for granuloma formation, a rare but significant cause of spinal cord compression from a granuloma mass formed at the catheter tip. Most pumps are MRI safe, but this information is difficult to obtain. Some pumps may have their valves forced open with an MRI. Hopefully, the patient's information card will say whether his pump is MRI-safe.

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Selection Criteria for Intrathecal Pump Implantation

  • Clear diagnosis
  • No psychological or sociological contraindications
  • Untreatable side effects of opioids (after opioid rotation)
  • Failure of several conservative treatments
  • Consider other interventional procedures (peripheral nerve blocks, neurolytic blockades, and cordotomy).
  • Life expectancy less than three to six months
  • Positive response during trial period
  • The patient understands the therapy; no cognitive disorders in patients under age 50.
  • Consider alternatives, including chronic pain rehabilitation programs.

Source: Pain Pract 2014;14(5):461.

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Medications Used in Intrathecal Pumps

FDA-Approved

  • Morphine*
  • Ziconotide (calcium channel blocker)
  • Baclofen

Not Approved by the FDA, Used Alone or in Combination

  • Fentanyl/Sufentanil*
  • Hydromorphone*
  • Midazolam
  • Bupivacaine
  • Clonidine
  • Meperidine

*Considered first-line therapy.

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Learning Objectives for This Month's CME Activity: After participating in this CME activity, readers should be better able to evaluate conditions and problems related to intrathecal pumps, particularly when patients suffer withdrawal, which can be severe or life-threatening.

Reader Feedback: Readers are invited to ask specific questions and offer personal experiences, comments, or observations on InFocus topics. Literature references are appreciated. Pertinent responses will be published in a future issue. Please send comments to emn@lww.com.

Dr. Roberts: You talk about not being arrogant with colleagues or patients in your September column, “How to Be a Real EP.” (EMN 2016;38[9:12; http://bit.ly/2cbFlHo.) Then you make the statement, “Even a pediatrician probably possesses some talents that you do not.” Are pediatricians as specialists in a separate category from “real” specialists?

As a pediatric-trained emergency physician, I think my skills at evaluating children are much better than the EP who spent only two to three months of training seeing children. There is a reason many hospitals are opening pediatric EDs. Parents and community physicians are not happy with many general EDs treating their patients.

Your pediatric colleagues do have skills that you do not. Your statement about “even a pediatrician” is disrespectful in an article that purports to give good advice to new graduates. We are there to answer questions and see concerning patients. We deserve your respect. — Deborah Callanan, MD, San Antonio

Dr. Roberts: This was a beautiful article, full of wisdom, but I take issue with the quote, “Even a pediatrician probably possesses some talents that you do not.” I am not God's gift to pediatrics, but many academic physicians at tertiary and quaternary care centers have a lot to offer in terms of talents, and do so making horrendously low salaries while living in expensive areas because they love kids and treat the sickest of the sick. Some train for six years to gain such knowledge, much longer than the average emergency physician. This attitude should not be tolerated in medicine. Back-handed compliments are not appreciated. Medicine is a team sport; everyone plays her part. — Liz Dorwart, DO, California

Dr. Roberts responds: My apologies, for sure. I did not intend to insult pediatricians, especially emergency-trained ones. What I meant was that pediatricians do indeed have more expertise in some areas, but I could have chosen a better way of saying that. And I should have removed the word “even” so that was clear.

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