American Society of Regional Anesthesia and Pain Medicine August 2016 - 32
PRO
Use of Ziconotide as First Line Intrathecal Therapy?
ZICONOTIDE SHOULD BE TRIED
BEFORE INTRATHECAL OPIOIDS
As a relative newcomer to the
field, one cannot help noticing
a palpable decline in the use of
intrathecal drug delivery systems
(IDDS) and the obvious lack of
comfort in implementing them
among the current generation
of practitioners. There is no
data to suggest why this is; one
can only speculate as to the
Corey W Hunter, MD
constellation of reasons leading
Executive Director
to this paradigm shift. These
Ainsworth Institute of Pain
reasons may include overdoseManagement
related deaths, low margin
New York, NY
for error, granulomas, high
maintenance, reliance on opioids,
Section Editor: Kevin Vorenkamp, MD
or just a high overall incidence of
complications. Of all the complications that can happen with IDDS,
the most common is related to the drug inside the pump.1,2
When discussing IDDS in present day pain management, phrases
such as "end-of-the-road" and "salvage therapy" are often
mentioned in the same breath. An end-of-the-road can come in
many forms but, more often than not, it involves accepting that
the only solution to a patient's problem is pharmacologic (typically
opioids), and the compromise is to simply provide those opioids in a
different form-intrathecally rather than orally. This is where many
pain doctors feel a conflict of conscience. The core philosophy of
an interventionalist, particularly a neuromodulator, is to solve a
patient's pain problem procedurally rather than pharmacologically.
Implementing IDDS with opioids can be a pyrrhic victory in that a
procedure was ultimately used to provide relief, yet opioids are still
at the core of it, albeit a different form of delivery.
Enter ziconotide. The molecule is a calcium channel blocker that
works intrathecally to inhibit the release of glutamate, calcitonin
gene-related peptide (CGRP), and substance P in the brain and
spinal cord to provide pain relief3,4; the best part is, it is not an
opioid. This alone should assuage fears many encounter when
considering IDDS that may ultimately lead them to consider other
options. Yet others can glean a sense of satisfaction by simply
being able to treat a patient's pain without opioids.
Philosophical reasons aside, there are two obvious advantages to
using ziconotide over opioids.
* Easier to trial - Ziconotide can be safely trialed in the office
setting via intrathecal (IT) bolus injections with the patient being
discharged home several hours later.5 Opioids, on the other
hand, carry a much larger side effect profile when given as an
32
2
IT bolus (ie, delayed onset respiratory depression), leading many
practitioners to admit trial patients overnight for monitoring or
simply resort to inpatient trials via epidural/IT infusion.6
* Better side effect profile - Ziconotide is an overall safer drug.
Granulomas and respiratory depression are not problems with
ziconotide as it is not an opioid. To date, there has not been a
single death reported with the use of ziconotide.3,7
COMPLICATIONS WITH OPIOIDS
* Granuloma formation (1.16% incidence)8 is consistently
associated with the use of opioids in the IT space.5,9,10 Most
granulomas will spontaneously regress with removal of the
opioids from the pump11; in fact, the Polyanalgesic Consensus
Committee (PACC) recommended in 2012 that if a patient
presents with a granuloma in the absence of neurological
deficits, the physician should switch to ziconotide.4
* Opioids can be absorbed orally, subcutaneously, intravenously,
and, of course, intrathecally. From 1996 to 2010, there
were 351 reports of pocket refills (inadvertent deposition of
medication outside the reservoir).12 With opioids, this can
lead to systemic toxicity and potential overdose-even death.
Ziconotide, on the other hand, has a limited ability to cross the
blood-brain barrier.13
* Patients are at risk for developing centrally mediated respiratory
depression, constipation, opioid-induced androgen deficiency
(OIAD),14 urinary retention, cognitive impairment, and headache.15
* There is a 7.5-fold increase in mortality over the first 3 days
after an IDDS-related procedure (which includes pump refill
and reprogramming) in patients with nonmalignant pain. While
the relative risk is highest immediately following the implant,
the highest numbers of deaths occur during the maintenancephase-this includes human error in the reprogramming phase
and pocket refills.16,17
COMPLICATIONS WITH ZICONOTIDE
* Common dose-related side effects include confusion, memory
impairment, speech disorder/aphasia, dizziness, blurred vision,
nystagmus, and sedation.4,18
* Patients may become unresponsive or stuporous (2%).19
* Severe psychiatric symptoms and neurologic impairment can
occur, including hallucinations (12%), paranoia (3%), hostility
(2%), delirium (2%), psychosis (1%), and mania (0.4%).16,20
PUBLIC PERCEPTION
As of 2014, pain relievers are the second-most commonly abused
drugs in the United States, with 4.3 million Americans using them
for nonmedical reasons.21 The number of those using pain relievers
for nonmedical reasons has remained relatively unchanged from
2002 to 2014; however, the number of deaths from prescription
drugs, namely opioids, is up threefold since 2001.22 At a time in
"Pro" continued on page 34
American Society of Regional Anesthesia and Pain Medicine
2016
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