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August 2011
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August/September 2011 Page 3
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Intrathecal Analgesia when injected intrathecally and are tion of bupivacaine in patients with
preferred. Table 1 displays the hy- malignant or nonmalignant pain
By Carla Jardin, PharmD
PGY2 Cardiology Resident drophilicity as well as the recom- who have failed IT morphine mono-
St. Luke’s Episcopal Hospital mended conversions for IT dosing therapy provides adequate pain
of opioid agents. Morphine, a highly relief in most subjects. Addition of
Intrathecal (intraspinal) analge- water-soluble opioid, is considered local anesthetics enhances analge-
sia is the delivery of pain medica- the first line opioid for IT analgesia; sic effects at a reduced opioid dos-
tions directly into the spinal col- however, it is also associated with es with fewer side effects. The rec-
umn. It is reserved for patients with higher rates of pruritis, vomiting, ommended dose of bupivacaine is
severe chronic pain who have failed between 3 – 50 mg/day, but can be
and respiratory depression than
all other routes and methods of an- tolerated up to doses > 100 mg/
other opiates. When compared to
algesia. Most clinical trials evaluat- day as reported in some case re-
oral and parenteral administration,
ing intrathecal (IT) analgesia are ports. The side effects most com-
the incidence of side effects with IT
studied in cancer patients. Not monly associated with IT bupiva-
dosing is significantly reduced. The
many studies have been performed caine include numbness, paresthe-
in patients with nonmalignant pain. most common side effects associat-
sias, weakness, and bowel or blad-
Prior to initiating IT analgesia, it is ed with IT opioids are constipation,
der dysfunction.
important to screen patients for urinary retention, nausea, vomiting, Alpha-2 agonists have also
signs of substance abuse or addic- and decreased libido. Opioids have been shown to provide analgesic
tion, aberrant behavior, and psycho- been shown effective in treating effects by binding to receptors on
logical conditions. IT analgesia can malignant and nociceptive pain, but primary afferent neurons thereby
be dangerous if doses are not ad- may not be as efficacious in treat- diminishing the release of neuro-
ministered appropriately or discon- ing neuropathic pain. transmitters which signal pain.
tinued abruptly. All IT therapy is ad- Although IT administration of Clonidine, the only FDA-approved IT
ministered via an intrathecal pump opioids is more effective in provid- alpha-2 agonist, has been shown in
device due to the very small doses ing pain relief than oral or parenter- multiple studies to have synergistic
of medications administered via al administration, often, patients analgesic properties with local an-
this route. Opioids, local anesthet- with severe chronic pain will require esthetics or opioids in patients with
ics, calcium channel blockers, al- additional agents for pain relief due malignant or nonmalignant pain.
pha-2 agonists, N-methyl-D- to limitations with adverse effects. However, conflicting studies show
aspartate (NMDA) receptor antago- As a result, local anesthetics have no additional benefit with clonidine.
nists, and gamma-aminobutyric ac- been combined with opioids to pro- The side effects noted with IT
id (GABA) agonists have been stud- vide more effective pain relief. Sev- clonidine use include sedation, hy-
ied for IT analgesia. eral studies have assessed the potension, nausea, and dry mouth.
Hydrophilic opioids are easily combination of IT bupivacaine and The addition of IT bupivacaine or IT
transported to neural receptors morphine and shown that the addi- clonidine to opioid analgesia is con-
Table 1. Conversion Ratios of Opioid Agonists1
sidered second line therapy where- and clonidine. Side effects most tioned in this article. It is important
as the combination of IT opioid, lo- commonly associated with IT mid- as a pharmacist to know the appro-
cal anesthetic, and clonidine is rec- azolam include sedation and motor priate dosing range for IT admin-
ommended as third line therapy. weakness at high doses. The gold- istration of these various agents
In patients with nociceptive en standard for treatment of spas- and ensure that parenteral doses
pain or those who have failed con- ticity is baclofen. In studies as- are not administered intrathecally.
ventional IT analgesia, ―N-type‖ and sessing baclofen’s ability to de- As pharmacists, we can also help
―L-type‖ calcium channel blockers crease muscle spasms, analgesic provide recommendations for com-
have been shown to alleviate pain. effects were noted and baclofen bination therapy and stepwise ap-
The only FDA-approved IT calcium was further studied and found to be proaches to escalate pain manage-
channel blocker is ziconatide, an ―N effective in providing pain relief in ment with the appropriate addition
-type‖ calcium channel blocker. Zi- patients with neuropathic pain, am- and combination of nonopioid anal-
conotide can be given as monother- putation, and plexopathy. The most gesics to previously failed opioid
apy, however it is commonly used in common side effects associated therapy. The ideal goal for IT anal-
combination with opioid and other with IT baclofen are drowsiness, gesia therapy is to provide ade-
nonopioid analgesics. Side effects cognitive impairment, weakness, quate pain relief while minimizing
commonly associated with ziconi- gastrointestinal upset and sexual side effects that limit quality of life.
tide are confusion, somnolence, dysfunction.
and urinary retention. Due to its If all other IT analgesia treat- References:
high cost and high incidence of side ment options have failed, the addi- Cohen SP and Dragovich A. In-
effects (up to 30%), ziconotide is tion of IT ketamine, an NMDA re- trathecal Analgesia. Anesthesiology
considered a fourth line agent for ceptor antagonist, can be used in Clin 2007;25:863-882.
chronic pain management. terminal patients. Ketamine use is
Additional agents, such as the reserved for the terminally ill due to Bennett G, Burchiel K, Buchser E, et
GABA agonists midazolam and bac- al. Clinical Guidelines for Intraspinal
the high risk of neurotoxicity. NDMA Infusion: Report of an Expert Panel.
lofen, can also be considered as receptors are upregulated after tis- J Pain Symptom Manage 2000;20
fourth line treatment of chronic sue injury and lower the threshold (2):S37-S43.
pain. GABA receptors, when activat- for painful stimulation. Ketamine
ed, decrease neuron excitability blocks NDMA receptors from bind-
and response to neurotransmitters
ing neurotransmitters relaying pain
signaling pain is diminished. IT mid-
signaling to the brain. The best evi-
azolam has been shown in several
dence supports use in cancer pa-
case reports to provide additional
tients with nociceptive and neuro-
pain relief in addition to IT opioids
pathic pain in combination with IT
Table 2. Dosing for IT Analgesics1 morphine, clonidine, and lidocaine
Drug Typical Dose Range or bupivacaine.
morphine 1-20 mg/day In patients with chronic pain
hydromorphone 0.5-10 mg/day there are many options for IT treat-
ment of pain. Table 2 contains the
fentanyl 0.02-0.3 mg/day
20-300 mcg/day dosing range commonly used for
bupivacaine 4-30 mg/day each of the analgesic agents men-
clonidine 0.03-1 mg/day
midazolam 0.2-6 mg/day
Area of Focus:
Direct patient care in Nutrition Support; Student and Resident training/Pharmacy Staff Development
in Nutrition Support/Critical Care; Safe practices for parenteral nutrition; Pharmacy mentoring and
leadership
Challenges:
The biggest challenge, by far, according to Todd in any career is work-life balance. Todd can honest-
ly say he does not regret any of his choices about the many professional opportunities in pharmacy
he has been presented, plus he says many are way more fun than they often sound at first. He has
Wake Forest University Baptist Medical Center in Win- seen most of the United States as a national speaker
ston-Salem, North Carolina. The research project I and active member of several professional organiza-
completed during my year at Wake Forest was eventu- tions, as well as met many of his closest friends, col-
ally published in Hospital Pharmacy. After residency I leagues and trainees over the last 23 years, as well as
was very fortunate to get a job offer at MD Anderson shared with his children. He wishes he had attended the
and I have worked here for the past four years. Being Landmark Education Forum before 2000 where he
involved in organizations helped me to network and gained the greatest insight into his own struggles both
develop leadership skills that lead me to where I am professionally and personally. According to Todd, he is
today. If you asked me 5 years ago, what would I be the possibility of inspirational leadership and admits
doing today, I don’t think I could have imagined where time is the only limiting factor to spread it around to eve-
my path has lead me. ryone he comes into contact with daily.