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Article Title
A PUBLICATION OF THE AMERICAN SOCIETY OF REGIONAL ANESTHESIA AND PAIN MEDICINE
In This Issue
On-the-Job Training: Learning Regional
Anesthesia in Private Practice - see page 6
American Society of Regional Anesthesia and Pain Medicine
12
Advancing the Science and Practice
of Regional Anesthesia and Pain Medicine
2012
Table of Contents
Message from the Executive Director __________________ 2
Editorial _________________________________________ 3
Evolution of Intrathecal Therapy: Patient-Centered Care ____ 4
Learning Regional Anesthesia in Private Practice _________ 6
Implications of the Fractured Spinal Needle _____________ 9
Spinal Cord Stimulation for Abdominal Pain ____________ 11
How I Do It: Lumbar Plexus Block ____________________ 15
Regional Anesthesia and Cancer Progression:
Basic Science Mechanisms _________________________ 17
Editor
Edward R. Mariano, M.D., M.A.S.
Newsletter Committee
Steven Orebaugh, M.D. (Regional Anesthesia Lead)
David Provenzano, M.D. (Pain Medicine Lead)
Michael Barrington, M.D.
Derek Dillane, M.D.
Jeff Gadsden, M.D.
Elizabeth Huntoon, M.D.
Robert Hurley, M.D., Ph.D.
Sandra Kopp, M.D.
Resident Section
David Webb, M.D.
Foreign Corresponding
Marc Van de Velde, M.D.
Herbert C. Spencer, M.D.
Officers
President: Joseph M. Neal, M.D.
Interim President-Elect: John C. Rowlingson, M.D.
Treasurer: Oscar A. De Leon Casasola, M.D.
Associate Treasurer: Marc A. Huntoon, M.D.
Past President: Vincent W.S. Chan, M.D.
Executive Director: Leonard Mafrica, MBA, CAE
Board of Directors
Honorio T. Benzon, M.D.
Asokumar Buvanendran, M.D.
Santhanam Suresh, M.D., F.A.A.P.
William F. Urmey, M.D.
Christopher L. Wu, M.D.
Eugene R. Viscusi, M.D.
Founding Fathers
L. Donald Bridenbaugh, M.D.
Harold Carron, M.D. (Deceased)
Jordan Katz, M.D.
P. Prithvi Raj, M.D.
Alon P. Winnie, M.D.
American Society of Regional Anesthesia and Pain Medicine
120 West Center Court • Schaumburg, IL • 60195-3169
phone: (847) 934-7246 • fax: (847) 740-2318 • www.asra.com
2
Copyright © 2012 American Society of Regional Anesthesia and Pain Medicine. All rights reserved.
Contents may not be reproduced without prior written permission of the publisher.
Message from the Executive Director
I’m Working for You
What do environmental engineers, high-tech service managers,
oncology nurses, and regional anesthesia and pain medicine
physicians have in common? More than one may think at first.
They all read peer-reviewed journals, attend professional
conferences, enjoy interacting with their peers, and most
importantly, they all care deeply about advancing their
profession. That’s why they join and actively contribute to the
activities of their professional societies. There’s one other thing
they have in common: they all belong to professional societies
that I have worked for as a staff executive.
I’m so pleased to have the opportunity to introduce myself to
you as the Executive
Director of ASRA. I
started in May 2012
after more than
30 years working
across these diverse
disciplines helping
dedicated volunteers
achieve their vision for the organizations that represent their
professions. I come to you with experience doing all the
things that professional societies do – publishing, scientific
conferences, web resources, education, advocacy, business
development, and strategic leadership.
In my role with ASRA, I work
with your Board of Directors to
prioritize and implement the
goals that will ultimately provide
you with educational resources,
tools, and programs that you
rely on for your personal and
professional growth. Some of
Leonard Mafrica, MBA, CAE
the things we are working on
Executive Director
right now, along with dedicated
ASRA committee members, are final details for the Fall Annual
Pain Medicine Meeting and the November Excellence in
Regional Anesthesia
Workshop, advanced
planning for the
2013 Spring Annual
Meeting, improving
financial reporting and
budgeting processes,
exploring new
educational products and services, and establishing a solid and
independent framework for business partnerships. At the same
time, we are thinking strategically about the future of ASRA,
from the development of new products and services to ensuring
that ASRA programming continues to be the most balanced and
comprehensive in the specialties we represent.
“I am here to make sure ASRA programs
and services meet your needs, and that your
questions and concerns are addressed.”
My role – and my goal – at ASRA is to help you achieve your
vision for the organization and to help each member gain
access to the rich resources offered by ASRA. Just as with the
other associations I’ve served, my background and training is
not the same as yours. I am not educated in your profession,
and I don’t claim to know much about your practice yet. What
I do know is how to deliver services that will help you learn
and grow. As with these other organizations, I don’t do it alone.
I’m backed by our Executive Assistant Karen Schneider in the
headquarters office and by the professional staff at Kenes
Associations Worldwide, a global association management
company that has the knowledge, expertise, and resources to
provide the highest quality conferences and member services to
our medical society clients around the world.
2
As the Executive Director for ASRA, I’m working for you. I am
here to make sure ASRA programs and services meet your
needs, and that your questions and concerns are addressed.
Please feel free to contact me any time at the headquarters
office or by email at [email protected].
American Society of Regional Anesthesia and Pain Medicine
2012
Editorial
I
n this issue of ASRA News, we
feature two excellent articles
by resident members, Drs.
Jules Huang and Ryan Perlman.
Dr. Huang presents an extremely
well-written review of the potential
role for multi-modal analgesia,
including regional anesthesia
techniques in reducing cancer
Edward R. Mariano, M.D., M.A.S. progression. This article provides
Editor
readers with a follow-up to Dr.
Palo Alto, CA
Marcel Durieux’s popular refresher
[email protected]
course lecture from the Spring
2012 Annual Meeting in San Diego. Dr. Perlman provides us with
a challenging case presentation that is sure to prompt some lively
discussion. When faced with a difficult spinal anesthetic, what
would you do if a piece of your needle was left behind?
For the past few months, I have been so impressed with the level
of involvement of our ASRA Resident Section Committee (RSC)
leadership. It has been a pleasure to work closely with the current
for residency in anesthesiology express interest in regional
anesthesia and pain medicine on applications and interviews.
Ideally, residents should get involved in ASRA as early as possible
to take full advantage of member benefits (e.g., discounted
membership fees, subscription to Regional Anesthesia and Pain
Medicine, ASRA News and E-News, members-only registration
rates to the annual meetings and workshops which feature
resident/fellow-only sessions, resident and fellow award
eligibility, and members-only content on the ASRA website). Yet,
many residency programs do not expose residents to regional
anesthesia or pain medicine specialty rotations well into the 2nd
or even 3rd year of residency. What can we do?
If you are at an academic center or affiliate and interact with
residents, actively encourage them to join ASRA. As a resident
advisor, you can get your advisees involved with your projects
and share some of the print and online publications from ASRA
with them so they can learn more about our specialty; then show
them how to sign up. Becoming an officer in the RSC requires
greater commitment but also provides motivated residents with
exposure to Society governance. The Chair-Elect and Chair of the
RSC participate on the Newsletter
Committee, writing and soliciting
articles, and the Chair serves on
the Annual Meeting Scientific and
Education Planning Committees,
helping to coordinate the resident/
fellow sessions.
“ I wish we could somehow bottle their energy and
enthusiasm and distribute it widely.”
RSC Chair, Dr. David Webb, and Dr. Art Flagg before him, on the
ASRA annual meeting scientific program and the newsletter, and
I look forward to working further with Dr. Huang as she assumes
the Chair position in the coming year. I think what impresses
me the most about these individuals is the fact that they have
committed additional time over their already-busy training
schedule to serve the Society so early in their careers. I wish we
could somehow bottle their energy and enthusiasm and distribute
it widely.
How do we get more residents involved in ASRA? The ASRA
Resident Section has been a formal part of the Society since
1995. It seems that more and more medical students applying
32
Taking the time to get residents involved in ASRA is a worthy
investment. Many of them will eventually pursue fellowship
training in regional anesthesia or pain medicine, advance our
specialty through scientific discovery, education, advocacy, and
clinical care, and gradually replace us as the leaders in the
Society.
Edward R. Mariano, M.D., M.A.S.
American Society of Regional Anesthesia and Pain Medicine
2012
Intrathecal Therapy:
Evolution towards a Patient-Centered Care Path
I
ntrathecal drug infusion is a cornerstone therapy in the
management of a number of refractory chronic pain
conditions. Intrathecal drug delivery systems (IDDS) allow
targeted drug delivery to receptor sites in the spinal canal,
thereby bypassing the blood brain barrier and first pass
metabolism. Colloquially known as “morphine pumps,” IDDS
have evolved from simple non-programmable pumps to more
elaborate electronically-controlled devices capable of delivering
complex regimens.1 The intrathecal agents themselves have
evolved from the traditional use of preservative-free morphine
to include a number of other agents. Whereas only two
intrathecal drugs are FDA-approved for pain relief (morphine
and the peptide ziconotide), a number of medications are used
intrathecally off-label. These include the opioids hydromorphone
and fentanyl, the local anesthetic bupivacaine, and the alpha-2
adrenergic agonist clonidine.2 Of note, intrathecal baclofen is
FDA-approved for the treatment of spasticity and has had only
anecdotal efficacy in analgesic applications.3
Indications for intrathecal therapy include refractory chronic
pain from cancer and non-cancer related conditions.4
Unfortunately, many patients with cancer-related pain have
advanced disease and limited survival time.5 Hence, the vast
majority of IDDS-implanted pain patients suffer from noncancer related pain with the most common diagnosis being
lumbar post-laminectomy syndrome also known as “failed back
surgery” syndrome.4
A number of parameters determine the analgesic efficacy
of intrathecal drug infusion therapy in patients with chronic
refractory pain. These include proper patient selection and
tailoring intrathecal agents and catheter position to patient’s
needs.6-8 Proper patient selection includes identification of a
pathological diagnosis that can explain the patient’s refractory
pain.7 In that regard, treatment of a patient with cancerrelated pain may entail different strategies than a patient
with non-cancer related pain.9,10 In addition, the candidate
patient should have a favorable psychological profile. This may
include absence of uncontrolled psychological disorders and
patient motivation to lead a healthier lifestyle such as smoking
cessation prior to pump trial.11 Additional patient characteristics
that are critical determinants of outcome include pre-implant
opioid dosage,12-14 patient age,6,12,14 and physical location of
majority of the pain.8 Indeed, patients on high doses of opioids
42
prior to IDDS placement require
larger doses of opioid for trial;
they not only require more
intrathecal opioid after implant
but also tend to have worse
pain scores.14 Hence, some have
advocated weaning off systemic
opioids prior to intrathecal pump
trial and implantation. This has
resulted in maintenance of
Salim Hayek, M.D., Ph.D.
Professor, Department of Anesthesiology
daily intrathecal morphine
Chief, Division of Pain Medicine
doses at 50-400 mcg/
Case Western Reserve University
day after IDDS implant and
Cleveland, OH
13
limited opioid tolerance.
Section Editor: David Provenzano, M.D.
However, weaning off opioids
may not be feasible in all patients (e.g., cancer pain patients).
Similar to oral opioid administration for chronic pain, intrathecal
opioid dose escalation often sets in as a result of tolerance
(non-cancer pain) and rarely consequent to disease progression
(cancer pain).6,8,12-19 Opioid dose escalation can be problematic
as it may lead to opioid-induced hyperalgesia20 and increases
the risk for development of intrathecal granulomas.21 Hence,
maneuvers aimed at blunting opioid dose escalation are
beneficial. These include selecting patients on low doses of
systemic opioids prior to trial,13 avoiding implantation of IDDS
in younger patients (<50 years old),6 and initiating bupivacaine
along with the opioid from the outset of intrathecal therapy.8
Animal studies and clinical experience with oral opioids in
chronic non-cancer pain suggest an age-dependent opioid
escalation whereby younger subjects escalate opioid dosage
and develop apparent tolerance at a much faster pace than
older subjects.22,23
Tailoring intrathecal drug delivery to patient characteristics
is critical to the success of therapy. The target sites of action
for most intrathecal agents reside in the superficial laminae
(substantia gelatinosa) of the dorsal horn of the spinal cord,
at a depth of 1-2 mm from the surface.24 For bupivacaine’s
analgesic effect, preferential targeting of sodium channels on
fila radicularia of sensory nerve rootlets prior to entering the
posterior aspects of the cord appears the likely mechanism of
action.25 Studies on a porcine model have shown much more
limited spread of intrathecal agents than previously thought
American Society of Regional Anesthesia and Pain Medicine
2012
3
Intrathecal Therapy:
Evolution towards a Patient-Centered Care Path continued...
and preferential drug penetration on the side of the cord closest
to the catheter.26,27 Hence, every effort should be made to target
the intrathecal catheter during IDDS placement to the posterior
intrathecal space in close proximity of putative drug target sites.
This is particularly important in conditions in which the pain is
localized to a fairly restricted dermatomal area, such as isolated
low back pain in patients with failed back surgery syndrome. In
such cases, catheter position is critical, especially when lipophilic
agents (which have restricted spread in the spinal space), such as
bupivacaine or fentanyl, are used.8
amendments to the less specific older consensus guidelines;
nonetheless, current treatment algorithms still specify the lines
of care based solely on the intrathecal agent. A patient-centered
algorithm of care is needed, based on patient diagnosis, as
suggested in Figure 1. Additional algorithms may be developed
that take into consideration the pain location and distribution and
consequently make evidence-based suggestions regarding best
medication options and optimal catheter localization. However,
large multi-center prospective studies must be performed to
validate these treatment recommendations.
The medical literature supporting the efficacy of intrathecal drug
delivery is limited.6 Hence, consensus statements have been
developed to guide physicians in the management of chronic pain
patients undergoing intrathecal therapy. There have been four
consensus statements since 2000.2,28-30 The latest polyanalgesic
consensus conference suggests different algorithms of care based
on whether the pain is nociceptive or neuropathic. Additionally,
Deer and colleagues recently published separate consensus
statements on cancer9 and non-cancer pain.10 These are welcome
References:
1. Krames ES. A history of intraspinal analgesia, a small and personal journey.
Neuromodulation : journal of the International Neuromodulation Society. May
2012;15(3):172-193.
2. Deer T, Krames ES, Hassenbusch SJ, et al. Polyanalgesic consensus conference
2007: recommendations for the management of pain by intrathecal (intraspinal)
drug delivery: report of an interdisciplinary expert panel. Neuromodulation :
journal of the International Neuromodulation Society. Oct 2007;10(4):300-328.
Figure 1:
Proposed patient-centered algorithmic
approach to consideration of intrathecal
drug delivery in chronic pain patients.
Different care paths are considered
for patients with cancer pain and for
those with non-cancer related pain.
Caution should be exercised prior to
the implantation of an intrathecal drug
delivery system in younger patients with
chronic non-cancer pain because of the
increased risk of development of opioid
tolerance and the increased need for
opioid dose escalations.6
5
American Society of Regional Anesthesia and Pain Medicine
2012
Intrathecal Therapy:
Evolution towards a Patient-Centered Care Path continued...
3. Saulino M, Burton AW, Danyo DA, Frost S, Glanzer J, Solanki DR. Intrathecal
ziconotide and baclofen provide pain relief in seven patients with neuropathic
pain and spasticity: case reports. European journal of physical and rehabilitation
medicine. Mar 2009;45(1):61-67.
4. Hayek SM, Deer TR, Pope JE, Panchal SJ, Patel VB. Intrathecal therapy for cancer
and non-cancer pain. Pain physician. May-Jun 2011;14(3):219-248.
5. Rauck RL, Cherry D, Boyer MF, Kosek P, Dunn J, Alo K. Long-term intrathecal
opioid therapy with a patient-activated, implanted delivery system for the
treatment of refractory cancer pain. The journal of pain : official journal of the
American Pain Society. Oct 2003;4(8):441-447.
6. Hayek SM, Veizi IE, Narouze SN, Mekhail N. Age-dependent intrathecal opioid
escalation in chronic noncancer pain patients. Pain Med. Aug 2011;12(8):
1179-1189.
7. Krames ES. Intraspinal opioid therapy for chronic nonmalignant pain: current
practice and clinical guidelines. Journal of pain and symptom management. Jun
1996;11(6):333-352.
8. Veizi IE, Hayek SM, Narouze S, Pope JE, Mekhail N. Combination of intrathecal
opioids with bupivacaine attenuates opioid dose escalation in chronic noncancer
pain patients. Pain Med. Oct 2011;12(10):1481-1489.
17. Rainov NG, Heidecke V, Burkert W. Long-term intrathecal infusion of drug
combinations for chronic back and leg pain. Journal of pain and symptom
management. Oct 2001;22(4):862-871.
18. Roberts LJ, Finch PM, Goucke CR, Price LM. Outcome of intrathecal opioids in
chronic non-cancer pain. Eur J Pain. 2001;5(4):353-361.
19. Shaladi A, Saltari MR, Piva B, et al. Continuous intrathecal morphine infusion in
patients with vertebral fractures due to osteoporosis. The Clinical journal of pain.
Jul-Aug 2007;23(6):511-517.
20. Forero M, Chan PS, Restrepo-Garces CE. Successful reversal of hyperalgesia/
myoclonus complex with low-dose ketamine infusion. Pain practice : the
official journal of World Institute of Pain. Feb 2012;12(2):154-158.
21. Deer TR. A prospective analysis of intrathecal granuloma in chronic pain
patients: a review of the literature and report of a surveillance study. Pain
physician. Apr 2004;7(2):225-228.
22. Buntin-Mushock C, Phillip L, Moriyama K, Palmer PP. Age-dependent
opioid escalation in chronic pain patients. Anesthesia and analgesia. Jun
2005;100(6):1740-1745.
23. Wang Y, Mitchell J, Moriyama K, et al. Age-dependent morphine tolerance
development in the rat. Anesthesia and analgesia. Jun 2005;100(6):1733-1739.
9. Deer TR, Smith HS, Burton AW, et al. Comprehensive consensus based guidelines
on intrathecal drug delivery systems in the treatment of pain caused by cancer
pain. Pain physician. May-Jun 2011;14(3):E283-312.
24. Kroin JS. Intrathecal drug administration. Present use and future trends.
Clinical pharmacokinetics. May 1992;22(5):319-326.
10. Deer TR, Smith HS, Cousins M, et al. Consensus guidelines for the selection
and implantation of patients with noncancer pain for intrathecal drug delivery.
Pain physician. May-Jun 2010;13(3):E175-213.
25. Hayek SM, Joseph PN, Mekhail NA. Pharmacology of intrathecally administered
agents for treatment of spasticity and pain. Seminars in Pain Medicine.
2003;1(4):238-253.
11. Deer TR, Prager J, Levy R, et al. Polyanalgesic Consensus Conference-2012:
Recommendations on Trialing for Intrathecal (Intraspinal) Drug Delivery:
Report of an Interdisciplinary Expert Panel. Neuromodulation : journal of the
International Neuromodulation Society. Apr 11 2012.
26. Bernards CM. Recent insights into the pharmacokinetics of spinal opioids
and the relevance to opioid selection. Current opinion in anaesthesiology. Oct
2004;17(5):441-447.
12. Dominguez E, Sahinler B, Bassam D, et al. Predictive value of intrathecal
narcotic trials for long-term therapy with implantable drug administration
systems in chronic non-cancer pain patients. Pain practice : the official journal
of World Institute of Pain. Dec 2002;2(4):315-325.
13. Grider JS, Harned ME, Etscheidt MA. Patient selection and outcomes using a
low-dose intrathecal opioid trialing method for chronic nonmalignant pain. Pain
physician. Jul-Aug 2011;14(4):343-351.
14. Kim D, Saidov A, Mandhare V, Shuster A. Role of pretrial systemic opioid
requirements, intrathecal trial dose, and non-psychological factors as
predictors of outcome for intrathecal pump therapy: one clinician’s
experience with lumbar postlaminectomy pain. Neuromodulation : journal
of the International Neuromodulation Society. Mar-Apr 2011;14(2):165-175;
discussion 175.
27. Bernards CM. Cerebrospinal fluid and spinal cord distribution of baclofen
and bupivacaine during slow intrathecal infusion in pigs. Anesthesiology. Jul
2006;105(1):169-178.
28. Bennett G, Burchiel K, Buchser E, et al. Clinical guidelines for intraspinal
infusion: report of an expert panel. PolyAnalgesic Consensus Conference 2000.
Journal of pain and symptom management. Aug 2000;20(2):S37-43.
29. Deer TR, Prager J, Levy R, et al. Polyanalgesic Consensus Conference 2012:
Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug
Delivery: Report of an Interdisciplinary Expert Panel. Neuromodulation : journal
of the International Neuromodulation Society. Jul 2 2012.
30. Hassenbusch SJ, Portenoy RK, Cousins M, et al. Polyanalgesic Consensus
Conference 2003: an update on the management of pain by intraspinal
drug delivery-- report of an expert panel. Journal of pain and symptom
management. Jun 2004;27(6):540-563.
15. Atli A, Theodore BR, Turk DC, Loeser JD. Intrathecal opioid therapy for chronic
nonmalignant pain: a retrospective cohort study with 3-year follow-up. Pain
Med. Jul 2010;11(7):1010-1016.
16. Paice JA, Penn RD, Shott S. Intraspinal morphine for chronic pain: a
retrospective, multicenter study. Journal of pain and symptom management.
Feb 1996;11(2):71-80.
62
American Society of Regional Anesthesia and Pain Medicine
2012
On-the-Job Training:
Learning Regional Anesthesia in Private Practice
[Medical education] is a life course, for which the work
of a few years under teachers is but a preparation.
Sir William Osler (1849-1919)
G
rowing evidence of patient benefits, along with the
acceptance and refinement of ultrasound-guidance, has
resulted in a recent renaissance in regional anesthesia
(RA). These factors, particularly when combined with an aging
population in need of orthopedic procedures, present everincreasing opportunities and demands for peripheral nerve
blocks in every practice environment. Experience with spinal
and epidural anesthesia during residency training produces a
sense of comfort with these procedures that continues upon
transitioning to private practice. However, such confidence is
usually not the case for peripheral nerve blocks.1 In this regard,
residency training can only realistically provide an introduction
to RA and a foundation for the ongoing study of the many
continually-evolving peripheral nerve block techniques.2
Unfortunately, anesthesiologists often lack a strategic approach
to the extended efforts necessary to attain some degree of
mastery in peripheral nerve blockade in the private practice
environment. Relegating this learning to random, trial-anderror experiences can be frustrating and ineffective; whereas
Figure 1: The experiential learning cycle (Adapted from:
Spencer J. Br Med J 2003;326:591-4).
a purposeful design can
transform this endeavor into
a thoughtful and deliberate
process. One framework
Brian E. Harrington, M.D.
Billings Clinic Hospital
that has been demonstrated
Billings, MT
to facilitate efficient and
Section Editor: Steven Orebaugh, M.D.
effective learning in the
clinical environment is the
experiential learning cycle (Figure 1).3
This article will briefly consider the individual stages of the
experiential learning cycle as they apply to learning peripheral
nerve blocks (both with and without ultrasound-guidance) in
private practice and will focus on general measures that can
be incorporated into virtually any busy clinical setting on a
daily basis.
CONCEPT
Actual performance of RA techniques should be preceded by
adequate instruction. After residency training, “real world”
didactics may come from a number of different sources.
1. Printed materials. Several types deserve special mention:
A) Textbooks. As traditional mainstays for learning RA,
textbooks reliably bridge the critical gap between anatomy
and successful block performance. Recently-published
texts usually cover both nerve stimulator and ultrasoundguided regional anesthesia (UGRA) techniques.
B) Subspecialty society communications. Regional anesthesia
societies naturally include education in their mission
statements and promote this process at every level. ASRA
News frequently contains authoritative contributions
that can be applied directly to private practice settings.
Recently, the American and European societies of RA
jointly published their recommendations for established
practitioners to begin to acquire the skill sets associated
with UGRA (the “Practice Pathway”).
72
American Society of Regional Anesthesia and Pain Medicine
2012
3
On-the-Job Training:
Learning Regional Anesthesia in Private Practice continued...
C) Selected journal articles. While many publications in the
anesthesiology literature are only marginally relevant to
private practitioners, review articles and those concerning
refinements of established techniques can be particularly
valuable. Somewhat paradoxically, experienced practitioners
with limited exposure to UGRA may find studies of novice
behavior in inexperienced residents to be quite germane.5
2. Internet resources. The expansion of computer networking has
resulted in nearly ubiquitous internet access. In the author’s
private practice, perhaps the most apparent advance in learning
has been the dissemination of instruction in peripheral nerve
block into the anesthesia workstation. Many websites (including
www.asra.com) now provide reliable, textbook-quality instruction
in RA. Timely expert video demonstrations for virtually all
regional procedures are also easily accessed on-line.
3. Colleagues. In the often solitary private practice setting,
practitioners are encouraged to consider their anesthesiology
colleagues as RA learning partners. Assisting or simply observing
a colleague perform a block (or vice versa) is a learning
opportunity. Partners who have recently completed residency
training may be particularly valuable in helping their department
attain proficiency in UGRA.
4. Anatomic study. Peripheral nerve anatomy and its variations can
be effectively reviewed through practice ultrasound scanning
of readily-available subjects (i.e., oneself and fellow healthcare
workers). This exercise also teaches and reinforces essential
scanning skills such as device operation, image optimization, and
image interpretation. Further proficiency in UGRA (e.g., needle
visualization) can be attained through the use of phantoms.6
1. Site preparation. A designated block area (ideally a “block
room”) can facilitate RA monitoring, sedation, and performance.7
A block cart allows specific supplies needed for RA (as well as
current recommendations for resuscitation from local anesthetic
systemic toxicity8) to be kept together in a single location.8
2. Standardized protocols. As often as possible, RA should
be integrated into routine patient care pathways (e.g., all
patients having a total knee arthroplasty will receive a femoral
nerve block).9 It must be emphasized, however, that any
standardization of RA techniques needs to include significant
ongoing input from anesthesiology colleagues and other
members of the patient care team.
3. Communication. The smooth incorporation of regional
procedures into daily practice requires proactive education
of patients, anesthesiology colleagues, surgeons, nurses,
and physical therapists. Designating one anesthesiologist as
the “regional anesthesia coordinator” can further encourage
effective communication.4
EXPERIENCE
RA procedures need to be performed within the “comfort zone”
of the operator, with an incremental progression toward more
advanced and difficult techniques.
1. Initial focus. To achieve a degree of expertise, practitioners with
limited experience should first concentrate on a few frequentlyperformed “core” techniques. Limiting the total number of
different blocks will help to more rapidly attain adequate
experience with specific procedures. In this regard, nearly
comprehensive coverage for most surgeries is possible with as
few as 6 peripheral techniques: 2 brachial plexus blocks (one
“Proper planning anticipates the application of concepts
into real-life experiences.”
PLANNING
Proper planning anticipates the application of concepts into
real-life experiences. In this context, this step must include the
creation of an environment that promotes the safe and efficient
performance of RA.
82
above and one below the clavicle), 1 thoracic (e.g. paravertebral)
block, 1 lower abdominal (e.g., transversus abdominis plane
[TAP]) block, and 2 lower extremity blocks (one femoral and one
sciatic).
American Society of Regional Anesthesia and Pain Medicine
2012
On-the-Job Training:
Learning Regional Anesthesia in Private Practice continued...
2. Eventual expansion. Since frequent experience is desirable
and essential to move through the cycle, anesthesiologists
should look for opportunities to appropriately expand their
routine performance of RA. In the author’s practice, this
has meant an evolution of RA beyond orthopedic surgery,
perhaps most noticeably into general surgery on the trunk
for such common procedures as breast lumpectomy (thoracic
paravertebral block),10 umbilical herniorraphy (rectus sheath
block),11 and inguinal herniorraphy (TAP block).12
REFLECTION
Reflecting on the performance of peripheral nerve blocks should
include a deliberate inventory of the learning process and
lessons learned.
1. Tracking experience. Maintaining a personal log book of RA
procedures (a practice of many residents during training) can
help extract maximal educational value from each block.
2. Patient feedback. An in-depth postoperative check, during
which patients can personally share their impressions of
RA, is an invaluable and underutilized learning aid. Only
after sufficient recovery (at least one day after surgery)
can individual patients meaningfully relate their level of
satisfaction with procedural sedation as well as block
efficacy and duration.
3. Professional development. Documenting and reporting
progress in RA performance is an excellent opportunity
to satisfy Maintenance of Certification in Anesthesiology
requirements (MOCA Part IV: Practice Performance
Assessment and Improvement; details can be found at:
References
1. Smith M, Sprung J, Zura A, et al. A survey of exposure to regional anesthesia
techniques in American anesthesia residency training programs. Reg Anesth
Pain Med 1999;24:11-6.
2. Kopacz DJ, Neal JM. Regional anesthesia and pain medicine: Residency
training - the year 2000. Reg Anesth Pain Med 2002;27:9-14.
3. Spencer J. Learning and teaching in the clinical environment. Br Med J
2003;326:591-4.
4. Sites B, Chan V, Neal J, et al. The ASRA and the ESRA Joint Committee
recommendations for education and training in ultrasound-guided regional
anesthesia. Reg Anesth Pain Med 2010;35:S74-S80.
5. O’Sullivan O, Aboulafia A, Iohom G, et al. Proactive error analysis of
ultrasound-guided axillary brachial plexus block performance. Reg Anesth
Pain Med 2011;36:502-7.
6. Hocking G, Hebard S, Mitchell C. A review of the benefits and pitfalls of
phantoms in ultrasound-guided regional anesthesia. Reg Anesth Pain Med
2011;36:162-70.
7. Armstrong KPJ, Cherry RA. Brachial plexus anesthesia compared to general
anesthesia when a block room is available. Can J Anesth 2004;51:41-4.
8. Neal JM, Mulroy MF, Weinberg GL. American Society of Regional Anesthesia
and Pain Medicine checklist for managing local anesthetic systemic toxicity:
2012 version. Reg Anesth Pain Med 2012;37:16-8.
9. Hebl JR, Dilger JA, Byer DE, et al. A pre-emptive multimodal pathway
featuring peripheral nerve block improves postoperative outcomes after
major orthopedic surgery. Reg Anesth Pain Med 2008;33:510-7.
10. Schnabel A, Reichl SU, Kranke P, et al. Efficacy and safety of paravertebral
blocks in breast surgery: a meta-analysis of randomized controlled trials. Br
J Anaesth 2010;105:842-52.
11. Gurnaney HG, Maxwell LG, Kraemer FW, et al. Prospective randomized
observer-blinded study comparing the analgesic efficacy of ultrasoundguided rectus sheath block and local anaesthetic infiltration for umbilical
hernia repair. Br J Anaesth 2011;107:790-5.
12. Young MJ, Gorlin AW, Modest VE, Quraishi SA. Clinical implications of
the transversus abdominis plane block in adults. Anesthesiol Res Pract
2012;2012:731645.
www.theABA.org).
CONCLUSION
Learning peripheral nerve blocks is a process that begins
during anesthesiology residency training but necessarily
continues throughout a private practice career. Consciously
employing a structured approach like the experiential learning
cycle can greatly facilitate this effort. Practitioners are
encouraged to consider how the stages of the experiential
learning cycle may best apply to their unique practice settings.
92
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at http://asra.com/e-news.php
American Society of Regional Anesthesia and Pain Medicine
2012
3
Clinical Implications of the Fractured Spinal Needle
Ryan Perlman, M.D.
ASRA Resident Section Committee,
CA-4 Resident
McGill University
Montreal, Quebec, Canada
Section Editor: Steven Orebaugh, M.D.
T
his type of case seems to always happen after-hours.
The patient was a 41 year old male, ASA 3 with severe
peripheral vascular disease, who had undergone multiple
previous surgeries, including a remote right femoral-popliteal
bypass, which was complicated by recurrent graft infections. He
presented with generalized malaise and right leg erythema that
was unresponsive to medical management, prompting an urgent
irrigation and debridement of the right leg. His height was 195
cm, body mass index (BMI) of 35 kg/m2, with no apparent spine
deformities. After the anesthesiologist and patient agreed on the
anesthetic plan, spinal anesthesia was attempted using a 27
gauge Whitacre needle via an introducer. Needle placement was
challenging, with multiple bony contacts and redirections. After
attempting the procedure for 10 minutes, the spinal needle was
withdrawn with an estimated 4 cm missing.
Dr. Lahey published the first report of broken spinal needles, or
“unhappy situations” as he put it, wherein a 22 gauge needle had
been broken and retrieved without any neurological sequelae.1
Abou-Shameh and colleagues quoted an incidence of broken and
retained spinal needles of 1 in 5000 spinal anesthetics after two
cases occurred in 20 years of practice.2 Only ten case reports
have been published in the literature to date. Nevertheless, critical
review of these reports reveals potential risk factors for needle
fracture including high BMI, needle length, bone contact, multiple
passes with the same needle, and removal of the spinal needle
through an introducer.
Over half of the published case reports occurred in obese patients
requiring longer-than-usual spinal needles. Three of them involved
the use of a needle >10 cm long, one of which was in a parturient
with BMI of 50 kg/m2. An urgent Cesarean section was scheduled
and multiple spinal attempts were made with a 25 gauge 9 cm
10
2
Whitacre needle followed by a 14 cm 27 gauge needle with which
the anesthetist had limited experience. The needle was fractured
in two places with 3 cm left within the subcutaneous tissue.3
In attempting to determine the incidence of needle deformation
during spinal anesthesia, one study examined the effects of
bone contact on tip damage. After a spinal block, the needle
tip was inspected under light microscopy. Of the 295 Quincke
spinal needles, 7% of needles with known contact with bone had
“unmistakable” tip damage, while lack of bone contact resulted in
an undamaged or “slightly bent” tip in 99% of cases.4 The authors
concluded that the tips of smaller-gauge spinal needles are
particularly vulnerable if they hit bone. Sitzman and colleagues
then studied whether or not a bent tip led to an increased rate of
needle deflection using Quincke, Whitacre, and Sprotte needles
of varying gauges.5 The authors discovered that the Quincke
deflected the most and Whitacre the least. Furthermore, a greater
degree of bend at the tip and smaller needle gauges were
associated with a greater deflection further down the shaft.5
Although the use of an introducer is often recommended, spinal
needle fractures have been reported with its use. The most
recent reported case was in a patient scheduled for Cesarean
section requiring multiple spinal attempts with a 27 gauge, 11.5
cm Whitacre needle through a 17 gauge Tuohy-tip needle that
resulted in 1 cm of the spinal needle missing after the procedure.
Although a radiograph revealed no needle inside the patient, it
was assumed that the spinal needle had been bent with bony
contact and sheared off after retraction through the Tuohy.6
The following recommendations based on the published case
reports may help prevent a fractured spinal needle: avoiding
disproportionate force in needle advancement, limiting the number
of passes with the same needle, using needles of appropriate
length, redirecting the spinal needle only when it is within the
introducer, and advancing the spinal needle with the stylet in
place.3-8 Some anesthesiologists have advocated for the use of a
combined spinal-epidural technique in those patients at high risk
for difficult spinal.9
Currently, there are no guidelines for the management of this
rare complication. The most common concern is traumatic
nerve damage from the retained spinal needle. Additional risks
include needle migration, granuloma formation, and infection.10-11
No acute neurological sequelae have been reported in any of
American Society of Regional Anesthesia and Pain Medicine
2012
Clinical Implications of the Fractured Spinal Needle continued...
the published case reports, perhaps due to the usual needle
location being posterior and lateral to the spinal canal. If
there is little to no risk of nerve injury, it is reasonable to
reassure these patients, encourage follow-up if they become
symptomatic, and warn them that they may trigger metal
detectors.
However, if concern about possible damage to nerves or other
structures remain, the clinician should request both a CT scan
and a neurosurgical consultation. If the decision is made to
proceed with the planned surgical procedure, the decision to
attempt the spinal again at another space or avoid it entirely
is best made jointly by the perioperative care team and the
patient. In most of the published cases, the retained needle
fragment was removed surgically immediately following the
scheduled operation.
In our case, the patient opted to continue with the planned
spinal anesthetic, which was successfully performed a
different interspace, and the urgent surgery was completed.
Postoperative CT scan revealed a 3.4 cm fragment, with a
J-hook deformity, lying inferior and posterior to the L3 spinous
Figure 1: A) Initial CT scan the day after surgery; B) Follow-up
CT scan 3 months postoperatively.
A
B
process, 3.1 cm deep to the skin surface with no evidence of
spinal canal penetration (Figure 1A). The patient chose not to
have the fragment surgically removed, and a repeat CT scan
three months later showed superficial migration of the needle
(Figure 1B). While radiology suggested an attempt at extraction,
neurosurgery elected to continue following the patient clinically,
and the patient was satisfied with this plan.
References
1. Lahey FH. The removal of broken spinal anesthesia needles. JAMA
1929;93(7):518-19.
2. Abou-Shameh MA, Lyons G, Roa A, Mushtaque S: Broken needle complicating
spinal anaesthesia. International Journal of Obstetric Anesthesia
2006;15(2):178.
3. Greenway MW, Vickers R. Broken micro-tip spinal needle. International
Journal of Obstetric Anesthesia 2009;18(3):295-6.
4. Jokinen MJ, Pitkanen, MT, Lehtonen E, Rosenberg PH. Deformed spinal
needle tips and associated dural perforations examined by scanning electron
microscopy. Acta Anaesthesiologica Scandinavica 1996;40:687-90.
5. Sitzman BT, Uncles DR. The effects of needle type, gauge, and tip bend on
spinal needle deflection. Anesth Analg. 1996;82(2):297-301.
6. Wendling AL, Wendling MT. Fractured small gauge needle during attempted
combined spinal–epidural anesthesia for cesarean delivery. Anesthesia &
Analgesia 2010;111(1):245.
7. Gentili ME, Nicol JB, Enel D, Marret E. Recovery of a broken spinal needle.
Reg Anesth Pain Med. 2006;31(2):186.
8. Cruvinel MG, Andrade AV. Needle fracture during spinal puncture. Rev. Bras.
Anestesiol 2004;54(6):794-98.
9. Teh J. Breakage of Whitacre 27 gauge needle during performance of spinal
anaesthesia for caesarean section. Anaesth Intensive Care 1997;25:1-96.
10. Ulloth JE, Haines SJ. Acupuncture needles causing lumbar cerebrospinal
fluid fistula. J Neurosurg Spine. 2007;6(6):567-9.
11. Rodney et al. Intraabdominal Abscess after Acupuncture. N Engl J Med
2004;350:1763.
11
2
American Society of Regional Anesthesia and Pain Medicine
2012
3
Spinal Cord Stimulation for Chronic Visceral Abdominal Pain
Ian M. Fowler, M.D., LCDR, MC, USN
Staff Pain Medicine Physician and
Anesthesiologist
Naval Medical Center San Diego
San Diego, California
Section Editor: Elizabeth Huntoon, M.D.
C
hronic abdominal pain affects up to 20% of the U.S.
population and often results in not only severe debilitating
pain, but also a myriad of other associated symptoms
including nausea, vomiting, and diarrhea.1 Although numerous
treatments are available for this pain, none have clearly
demonstrated sustained or reliable efficacy in pain reduction
or functional improvement.2,3 Until recently, the main treatment
options were pharmacologic, diet alteration, and psychotherapy.4
Invasive techniques including various sympathetic nerve blocks,
radiofrequency treatments to these nerves, and surgery have
not demonstrated positive long-term outcomes.4-6 Furthermore,
three additional characteristics of this chronic pain syndrome may
contribute to its poor outcome to treatments. These include: 1)
a strong association with psychological disorders and a history
of physical or sexual abuse;6,7 2) a wide diversity of etiologies
including functional bowel disorders, pancreatitis, adhesions, and
mesenteric ischemia;6,9 and 3) a poorly understood mechanism
of pathophysiology.10,11 In light of these three characteristics and
ineffective treatments, chronic abdominal pain patients create
a significant burden on the healthcare system and are at risk of
developing psychosocial and/or physical impairment.1
Spinal cord stimulation (SCS) has been used for the treatment
of various neuropathic and ischemic pain conditions, and its
use for the treatment of conditions like complex regional pain
syndrome12 and failed back surgery syndrome13 has been welldescribed. The use of this technology for the treatment of visceral
pain syndromes, however, is relatively new and, until recently,
a novel concept. Ceballos, et al.14 first reported using SCS for
the successful treatment of chronic, intractable abdominal
pain secondary to mesenteric ischemia. Since this initial case
report, numerous additional case reports,14-22 two retrospective
reviews,6,23 and a national survey of pain management physicians
12
2
using SCS for the treatment of chronic abdominal pain24 have
been published (Table 1). The most exciting and promising aspect
of this recent surge in publications is that each piece of literature
suggests favorable results.
Case reports describing the use of SCS for treatment of irritable
bowel syndrome (IBS),15,22 mesenteric ischemia,14,21 chronic
pancreatitis,16,19,20 chronic postsurgical pain,16,17 and even
abdominal pain exacerbations from Familial Mediterranean Fever18
have all been reported. Four recurring attributes were present
in most of these case reports. First, patients demonstrated
considerable suffering despite maximal medication therapy
including moderate to high dose opioids and other analgesics and,
in many instances, were heavily utilizing the health care system
in a desire to obtain pain relief. Second, the authors in over half
of the case reports reported trying some form of sympathetic
block prior to considering SCS. Moreover, nearly all of the patients
who received these sympathetic blocks had temporary pain relief
and then subsequently had successful SCS trials and implants.
Third, lead tip placement most commonly was at the T6 vertebral
level, but ranged from T2-T9 (Figure 1). Fourth, all of the patients
reported reduction in pain; interestingly, patients with a functional
component to their pain (e.g., diarrhea, nausea) reported a
decrease in these symptoms as well. The results of these case
reports suggest that SCS with lead placement in the mid-thoracic
spine region may be a viable treatment option for various types of
chronic abdominal pain and that there may be some association
between a positive response to sympathetic blocks and successful
SCS trial, a concept previously described by Hord, et al.25
Two recent retrospective reviews in 2010 and 2011 and a
national survey of pain providers provide the most convincing
evidence, thus far, for the use of SCS for chronic abdominal pain.
Kapural, et al.6 reviewed the records of 35 consecutive patients
who were trialed with SCS for chronic visceral abdominal pain
(28 underwent implantation) and demonstrated a greater than
50% reduction in VAS scores and greater than 60% reduction in
opioid use at one year follow-up. Furthermore, Kapural et al.23
performed an additional retrospective review of 30 consecutive
patients with chronic pancreatitis who were trialed with SCS (24
underwent implantation) and demonstrated a 50% reduction in
VAS scores and 60% reduction in opioid use at one year followup. Two additional results of these reviews should be mentioned.
First, most of the patients who failed the SCS trial also failed to
American Society of Regional Anesthesia and Pain Medicine
2012
Spinal Cord Stimulation for Chronic Visceral Abdominal Pain continued...
Table 1: Summary of literature for the use of SCS for chronic abdominal pain
Authors
Year
#
Condition* Literature
Type
Sympathetic
Blocks**
Result of Lead Tip
Block
Results
Complications
Follow Up
Ceballos, et al.14
2000
1
MI
Case Report
CP
Temp
T6
None reported
11 mos
Krames &
Mousad15
2004
1
IBS
Case Report
CP
No
T8
None reported
6 mos
Khan, Raza, &
Khan16
2005
9
CP (5);
PSP (4)
Case Report
CP
Temp
T5 - T7
Tiede, et al.17
2006
2
PSP
Case Report
CP
Temp
T2
Kapur, Mutagi, &
Raphael18
2006
2
FMF
Case Report
None
N/A
T6-T9
Kapural & Rakic19
2008
1
CP
Case Report
CP
Temp
T6
Kim, et al.20
2009
1
CP
Case Report
None
No
T6-T8
Caruso, et al.21
2011
1
MI
Case Report
None
N/A
T4-6
Reduced pain,
complete wean of
opioids, improved sleep
and function
Reduced pain,
decreased diarrheal
epidsodes, decreased
opioid use
Mean reduction in
VAS of 4.9, > 50%
reduction in opioid use
70-80% reduction in
pain, decreased opioid
use, return to work
Pain reduction,
complete wean of
opioids, return to work
Pain reduction,
decrease in pain
disability index,
complete wean of
opioids
50% pain reduction,
decreased pain rating
index, decreased
functional disability,
return to work
75% pain reduction,
decreased opioid use
Rana & Knezevic22 2012
1
IBS
Case Report
None
N/A
T8
Kapural, Cywinski, 2011
Sparks23
30
CP
Retrospective
review
SPL or CP
Temp
T4-T6
Kapural, et al.6
35
MI(1);
CP(26);
PSP (8)
Retrospective
review
SPL, CP or
SHP
Temp
(most)
T4-T12
2010
Reduced pain, better
mgt of GI symptoms
50% reduction in VAS
scores, 60% reduction
in morphine equivalents
at 1 year
> 50% reduction in
VAS scores, > 60%
reduction in morphine
equivalents at 1 year
Lead migration in > 1 yr
1 patient
Lead migration in 4 mos
1 patient
None reported
3 yrs (1);
3 mos (1)
None reported
3 mos
None reported
14 mos
One adverse
event (not
specified)
None reported
15 days
1 yr
Infection (2); Lead 1 yr
migration (1)
Infection (3); Lead 1 yr
migration (1)
*MI (mesenteric ischemia); IBS (irritable bowel syndrome); PSP (postsurgical pain); CP (chronic pancreatitis); FMF (Familial Mediterranean Fever)
**CP (celiac plexus); SPL (splanchnic nerve); SHP (superior hypogastric plexus).
respond to sympathetic blocks prior to trial. Although this may
suggest that a positive response to sympathetic blocks may
predict a positive response to SCS trial, the sample size is too
small to make this assertion. Second, lead tip placement was
most commonly at T5 or T6, regardless of the condition being
treated, and there was no difference in pain scores amongst
patients who were implanted with 1, 2, or 3 leads. Additionally,
Kapural et al.24 conducted a survey of pain physicians who
use SCS for chronic visceral abdominal pain and reported the
following results from the 23 physicians who returned surveys:
1) 66 of the 70 patients qualified for implantation after trial; 2)
13
2
66% reduction in VAS scores; 3) 77% reduction in opioid use at
last patient visit; 4) average patient follow-up of 84 weeks; and
5) lead tip positioning was T5 or T6. Thus, Dr. Kapural’s recent
publications augment the previously-published case report
results and show compelling evidence for SCS in the treatment
of chronic abdominal pain.
Although the current evidence seems promising, one must
consider several factors before utilizing this technology for
chronic abdominal pain. The evidence remains limited in that
no prospective, randomized trials have been performed and
American Society of Regional Anesthesia and Pain Medicine
2012
3
Spinal Cord Stimulation for Chronic Visceral Abdominal Pain continued...
the published retrospective reviews are subject to selection
bias. Psychosocial dysfunction or medication misuse must be
addressed prior to consideration of an implantable technology.
Most importantly, appropriate selection of patients is the key to
success, particularly with a new treatment for a pain condition
that is often refractory to other therapies. Deer and Masone26 and
Kapural, et al.6 both emphasize that proper selection of patients
is likely the key to both successful short-term and long-term
outcomes. By keeping these limitations in mind and, in light of the
positive emerging evidence, SCS has the potential to be a reliable,
efficacious, and long-term solution for patients with intractable
visceral abdominal pain.
References:
Disclaimer: The views expressed in this article are those of the
author and do not necessarily reflect the official policy or position
of the Department of the Navy, Department of Defense, or the
U.S. Government.
7. Nicolai MP, Fidder HH, Beck JJ, Bekker MD, Putter H, Pelger RC, Van Driel MF,
Elzevier HW. Sexual abuse history in GI illness, how do gastroenterologists deal
with it? J Sex Med 2012; 9: 1277-84.
Figure 1: Anterior-Posterior radiographic view of thoracic spine
demonstrating placement of tips of two octapolar leads at the
superior endplate of the T7 vertebral body in a patient with
chronic abdominal pain and irritable bowel syndrome.
9. Soykan I, Sivri B, Sarosiek I, Kiernan B, McCallum RW. Demography, clinical
characteristics, psychological and abuse profiles, treatment, and long-term
follow-up of patients with gastroparesis. Dig Dis Sci 1998; 43: 2398-404.
1. Russo MW, Wei JT, Thiny MT, Gangarosa LM, Brown A, Ringel Y, Shaheen NJ,
Sandler RS. Digestive and liver diseases statistics, 2004. Gastroenterology 2004;
126: 1448-53.
2. Galili O, Shaoul R, Mogilner J. Treatment of chronic recurrent abdominal pain:
laparascopy or hypnosis? J Laparoendoscop Adv Surg Tech A 2009; 19: 93-6.
3. Dorn SD, Meek PD, Shah ND. Increasing frequency of opioid prescriptions for
chronic abdominal pain in US outpatient clinics. Clin Gastroenterol Hepatol 2011;
9: 1078-85.
4. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC.
Functional bowel disorders. Gastroenterology 2006; 130: 1480-91.
5. Raj PP, Sahinler B, Lowe M. Radiofrequency lesioning of splanchnic nerves. Pain
Pract 2002; 2: 241-7.
6. Kapural L, Nagem H, Tlucek H, Sessler DI. Spinal cord stimulation for chronic
visceral abdominal pain. Pain Med 2010; 11: 347-55.
8. Bonomi AE, Anderson ML, Reid RJ, Rivara FP, Carrell D, Thompson RS. Medical
and psychological diagnoses in women with a history of intimate partner
violence. Arch Intern Med 2009; 169: 1692-7.
10. Greenwood-Van Meerveld B, Johnson AC, Foreman RD, Linderoth B. Attenuation
by spinal cord stimulation of a nociceptive reflex generated by colorectal
distension in a rat model. Auton Neurosci 2003;104: 17-24.
11. Krames E, Foreman R. Spinal cord stimulation modulates visceral nociception
and hyperalgesia via the spinothalamic tracts and the postsynaptic dorsal
column pathways: a literature review and hypothesis. Neuromodulation 2007;
10: 224-37.
12. Kemler MA, De Vet HC, Barendse GA, Van DenWildenberg FA, Van Kleef M. The
effect of spinal cord stimulation in patients with chronic reflex sympathetic
dystrophy: Two years’ follow-up of the randomized controlled trial. Ann Neurol
2004;55:13–18.
13. Kumar K, Taylor RS, Jacques L, et al. Spinal cord stimulation versus
conventional medical management for neuropathic pain: A multicentre
randomised controlled trial in patients with failed back surgery syndrome. Pain
2007;132:179–88.
14. Ceballos A, Cabezudo L, Bovaira M, Fenollosa P, Moro B. Spinal cord
stimulation: a possible therapeutic alternative for chronic mesenteric
ischaemia. Pain 2000;87:99–101.
15. Krames E, Mousad DG. Spinal cord stimulation reverses pain and diarrheal
episodes of irritable bowel syndrome: a case report. Neuromodulation 2004; 7:
82-8.
16. Khan YN, Raza SS, Khan EA. Application of spinal cord stimulation for the
treatment of abdominal visceral pain syndrome: case reports. Neuromodulation
2005; 8: 14-27.
17. Tiede JM, Ghazi SM, Lamer TJ. The use of spinal cord stimulation in refractory
abdominal visceral pain: case reports and literature review. Pain Pract 2006; 6:
197-202.
14
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American Society of Regional Anesthesia and Pain Medicine
2012
Spinal Cord Stimulation for Chronic Visceral Abdominal Pain continued...
18. Kapur S, Mutagi H, Raphael J. Spinal cord stimulation for relief of abdominal
pain in two patients with familial mediterranean fever. Br J Anaesth 2006; 97:
866-8.
19. Kapural L, Rakic M. Spinal cord stimulation for chronic visceral pain secondary
to chronic non-alcoholic pancreatitis. J Clin Gastroenterol 2008; 42: 750-1.
20. Kim JK, Hong SH, Kim MH, Lee JK. Spinal cord stimulation for intractable
visceral pain due to chronic pancreatitis. J Korean Neurosurg Soc 2009; 46:
165-7.
21. Caruso C, Lo Sapio D, Ragosa V, Lo Sapio S, Cafora C, Romano L. Abdominal
angina due to obstruction of mesenteric artery treated with spinal cord
stimulation: a clinical case. Neuromodulation 2011; 14:146-50.
23. Kapural L, Cywinski JB, Sparks DA. Spinal cord stimulation for visceral pain
from chronic pancreatitis. Neuromodulation 2011; 14: 423-7.
24. Kapural L, Deer T, Yakovlev A, Bensitel T, Hayek S, Pyles S, Khan Y, Kapural A,
Cooper D, Stearns L, Zovic P. Technical aspects of spinal cord stimulation for
managing chronic visceral abdominal pain: the results of the national survey.
Pain Med 2010; 11: 685-91.
25. Hord ED, Cohen SP, Cosgrove CR, Ahmed SU, Vallejo R, Chang Y, Stojanovic
MP. The predictive value of sympathetic block for the success of spinal cord
stimulation. Neurosurgery 2003; 53: 626-33.
26. Deer T, Masone RJ. Selection of spinal cord stimulation candidates for the
treatment of chronic pain. Pain Med 2008; 9(S1): S82-S92.
22. Rana MV, Knezevic NN. Tripolar spinal cord stimulation for the treatment of
abdominal pain associated with irritable bowel syndrome. Neuromodulation
2012 Apr 11 [Epub ahead of print]
15
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American Society of Regional Anesthesia and Pain Medicine
2012
SAM-PM – Self-Assessment Module
Pain Medicine
Test your knowledge of Pain Medicine with SAM-PM.
Designed to assist with the completion of the subspecialty
certificate requirements for Maintenance of Certification in
Pain Medicine, SAM-PM is an online self-assessment tool
consisting of 100 questions with detailed answers to assess
multidisciplinary knowledge in pain medicine. The expertise
of several disciplines is brought together in an effort to
provide maximum benefits and allow you to earn up to
30 AMA Category 1 CreditsTM.
To learn more and order your module today, visit education.asahq.org/12SAMPM
or for questions, call (847) 825-5586.
This program is a collaboration between:
American Society of
Regional Anesthesia and Pain Medicine
American Society of Anesthesiologists
Accreditation and Credit Designation
This CME activity is sponsored by the American Society of Anesthesiologists.
The American Society of Anesthesiologists is accredited by the Accreditation Council for Continuing Medical Education
(ACCME) to provide continuing medical education for physicians.
The American Society of Anesthesiologists designates this enduring material for a maximum of 30 AMA PRA Category 1 Credit(s)™.
Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Maintenance of Care in Anesthesiology Program® and MOCA® are registered certification marks of the American Board of Anesthesiology®.
This self-assessment activity helps fulfill the self-assessment CME requirement for Part II of the Maintenance of Certification in Anesthesiology
Program (MOCA) of the American Board of Anesthesiology (ABA). Please consult the ABA website, www.ABA.org, for a list of all MOCA requirements.
Select, track and claim credit for CME courses with the ASA Education Center.
Visit education.asahq.org to register.
How I Do It: Posterior Lumbar Plexus Block
Jessen Mukalel, M.D.
Assistant Professor of Anesthesiology
Regional Anesthesia and Acute Pain Medicine
Fellowship Program Director
University of Texas at Houston, Memorial
Hermann Medical Center
Houston, TX
T
he posterior lumbar plexus block, also known as the psoas
compartment block (PCB), is a consistent and reliable block
for surgeries of the hip, thigh and knee as it anesthetizes
the lateral femoral cutaneous (posterior division of the ventral
rami of L2,3), femoral (posterior division of the ventral rami of L2,3,4)
and obturator (anterior division of the ventral rami of L2,3,4) nerves
within the psoas major muscle. In their cadaveric and computed
tomography (CT) studies, Farny and colleagues demonstrated the
intra-psoas location of the lumbar plexus at the level of the L4-5
intervertebral disc between the posterior 1/3 and anterior 2/3 of
the muscle.1 The anterior portion of the muscle arises from the
antero-lateral part of the vertebral bodies and the intervertebral
disc, while the posterior, or accessory part, originates from
the anterior aspect of the transverse process. They found the
lateral femoral cutaneous and femoral nerves to be in consistent
relationship in the same fascial plane, while the obturator nerve
location was more variable, sometimes in a fold of the psoas
muscle separate from the other nerves, although still blocked 92%
of the time. The same researchers found, using CT at the L4,5 level,
that the average depth of the skin to transverse process (TP), was
7.0 cm in females and 7.5 cm in males, with 2 cm on average
from TP to the plexus.
One clear advantage of the posterior approach to the PCB is the
preoperative placement of a perineural catheter (CPCB) away
from the surgical field as opposed to anterior techniques. CPCB
has been shown to be as effective as epidural block for analgesia
after total hip arthoplasty (THA) but with less nausea, urinary
retention, motor block, and orthostatic hypotension.2 CPCB may
offer an additional advantage over epidural for THA by sparing the
contralateral leg.
17
2
NERvE STImULATION TEChNIQUE3
Once the patient is monitored, sedated, and positioned lateral
decubitus with the operative side up, the intercristal line and
the interspinous line are drawn. A mark is made 4.5 cm on the
intercristal line from the interspinous line toward the operative
side. After subcutaneous local anesthesia is given at the mark, a
25 gauge pencil-point spinal needle is introduced perpendicular to
the skin to find the L4 TP. If the TP is not contacted, the needle is
redirected in a cranial/caudal direction until TP depth is obtained.
Once found, the spinal needle is removed and that depth is
marked onto an 18 gauge, 10 cm stimulating Touhy-tip needle.
The Touhy needle is introduced at the same angle and depth as
the spinal needle with the bevel directed posterior-lateral, until
the TP is contacted. The needle is withdrawn and redirected
caudal to the TP and advanced up to a maximum of 2 cm (past the
depth to TP), with a current of 1.5 mA to elicit a quadriceps twitch,
then titrated down to between 0.3 to 0.5 mA while maintaining
the twitch. A sciatic or obturator nerve twitch is associated with
epidural/intrathecal spread,4,5 implying a needle tip placement
that is too medial. After proper needle placement, a 20 ml bolus
of 0.2% ropivacaine is administered through the needle with
aspiration for blood before every 5 ml. A 20 gauge catheter is
inserted through the Touhy needle 2-4cm past the needle tip. The
needle is removed and the catheter secured. A dilute infusion of
bupivacaine or ropivacaine at 6 ml/hr is started after surgery and
continued for two days with adjunct oral and IV pain medications.
ULTRASOUNd-GUIdEd TEChNIQUE
Karmakar and colleagues have described the parasagittal
technique6 using a low frequency (2-5 MHz) curvi-linear
transducer placed 3-4 cm lateral and parallel to the lumbar spine
to visualize the classic “trident” sign (L2,3,4 transverse processes;
Figure 1). A stimulating needle can be inserted and advanced
in-plane to the space between the L3 and L4 transverse processes
where the posterior portion of the lumbar plexus lies. Using a
probe with tissue harmonic imaging, the actual lumbar plexus may
occasionally be visualized.6 The major limitation of this technique
is the inability to visualize the needle shaft throughout the process
due to a necessary steep angulation to enter caudal to the TP.
For catheter insertion, rotate the bevel for a Touhy needle in the
posterior-lateral direction away from the intervertebral foramen to
avoid unintentional neuraxial catheterization.
American Society of Regional Anesthesia and Pain Medicine
2012
How I Do It: Posterior Lumbar Plexus Block continued...
Figure 1: Parasagittal ultrasound image using a low frequency
curvi-linear transducer; TP=Transverse Process; P=Psoas Major
muscle; ES=Erector Spinae muscle.
in a standardized fashion with the minimum number of needle
passes.
Table 1: Historical approaches to the PCB.
Author
Anatomical location to
transverse process (TP)
Comments
Winnie13
L4-5; intersection of PSIS
and intercristal line to L4 TP,
caudal direction with 15%
medial angulation, using loss of
resistance technique
L4-5; intercristal line, 3cm caudal
and 5cm lateral from midline to
L5 TP, cephalad direction
Medial angulation
may predispose to
neuraxial migration
of injectate or
catheter
88% incidence of
bilateral block per
Dalens 21
L4-5; intercristal line, 3cm caudal
and 3cm lateral from midline (2
cm medial to the original Chayen
approach) to L5 TP, cephalad
direction
Cephalad needle
angulation makes
it challenging to
thread catheters in
a posterior-lateral
direction
Only limitation is the
occasional inability to
palpate the PSIS on
obese patients.
Chayen14
Pandin (Modified
Chayen)8
POTENTIAL COmPLICATIONS
Complications associated with the PCB include: local anesthetic
toxicity (2/394),7 paresthesia (41/132),8 epidural/intrathecal
spread (2/132),8 and retroperitoneal hematoma and renal
puncture.9 Bilateral spread is a side effect, occuring 20-30%
of the time without serious complications. This may be related
to high volume of injectate (>20 ml)10 with spread along the
prevertebral fascia or subdural space rather than the epidural
or intrathecal space. Local anesthetic toxicity may occur
as well as bleeding in a non-compressible area. Therefore,
ASRA anticoagulation guidelines for neuraxial block should be
applied.11 If real-time ultrasound guidance is not employed
for catheter placement, prepuncture ultrasound scanning to
confirm proper needle insertion site and estimate the depth to
the transverse process,12 or use of a “finder” pencil-point spinal
needle to determine transverse process depth when ultrasound
is not available, is advised.
RECOmmENdATIONS
The posterior PCB is an effective analgesic block for hip
arthroplasty and a useful block for continuous analgesia for
fractures above the mid femur, as well as other surgeries
of the thigh and hip. As part of a clinical pathway, this block
can help facilitate short-term functional recovery and timely
discharge eligibility. I generally keep the catheter in place for
2 days after hip arthroplasty, allowing earlier ambulation and
preservation of contralateral leg strength. I believe that this is
a safe block which is readily accomplished when conducted
18
2
Capdevila
L4 spinous process; junction
(Modified Winnie)3 of the lateral third and medial
two-thirds of a line between
the spinous process of L4 (1cm
above the intercristal line) and a
line parallel to the spinal column
passing through the PSIS to L4
TP, caudal direction
Table 2: Hip innervation.
Innervation of the hip
Nerve innervation
Medial hip joint capsule
Obturator nerve articular branches
Anterior hip joint capsule
Femoral nerve articular branches
Posterior hip joint capsule
Superior gluteal nerve, sciatic nerve, and nerve
to the quadratus femoris muscle
ACkNOwLEdGmENTS
Special thanks to Alfonso Altamirano for his help with
the illustration.
References
1. Farny J, Drolet P, Girard M. Anatomy of the posterior approach to the lumbar
plexus block. Can J Anaesth 1994;41:480-5.
2. Turker G, Uckunkaya N, Yavascaoglu B, Yilmazlar A, Ozcelik S. Comparison
of the catheter-technique psoas compartment block and the epidural block
for analgesia in partial hip replacement surgery. Acta Anaesthesiol Scand
2003;47:30-6.
3. Capdevila X, Macaire P, Dadure C, Choquet O, Biboulet P, Ryckwaert Y, D’Athis
F. Continuous psoas compartment block for postoperative analgesia after
total hip arthroplasty: new landmarks, technical guidelines, and clinical
evaluation. Anesth Analg 2002;94:1606-13.
4. Dalens B, Tanguy A, Vanneuville G. Lumbar plexus block in children: a
comparison of two procedures in 50 patients. Anesth Analg 1988;67:750-8.
American Society of Regional Anesthesia and Pain Medicine
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How I Do It: Posterior Lumbar Plexus Block continued...
5. Cesur M, Alici HA, Erdem AF. A plantar flexion response to nerve stimulation
indicates needle misplacement in the epidural/spinal space during psoas
compartment block. J Anesth 2009;23:139-42.
6. Karmakar MK, Ho AM, Li X, Kwok WH, Tsang K, Ngan Kee WD. Ultrasound-guided
lumbar plexus block through the acoustic window of the lumbar ultrasound
trident. Br J Anaesth 2008;100:533-7.
7. Auroy Y, Benhamou D, Bargues L, Ecoffey C, Falissard B, Mercier FJ, Bouaziz H,
Samii K. Major complications of regional anesthesia in France: The SOS Regional
Anesthesia Hotline Service. Anesthesiology 2002;97:1274-80.
8. Pandin PC, Vandesteene A, d’Hollander AA. Lumbar plexus posterior approach: a
catheter placement description using electrical nerve stimulation. Anesth Analg
2002;95:1428-31.
9. Mannion S. Psoas compartment block. Continuing Education in Anaesthesia,
Critical Care & Pain J 2007;7:162-6.
11. Horlocker TT, Wedel DJ, Rowlingson JC, Enneking FK, Kopp SL, Benzon HT,
Brown DL, Heit JA, Mulroy MF, Rosenquist RW, Tryba M, Yuan CS. Regional
anesthesia in the patient receiving antithrombotic or thrombolytic therapy:
American Society of Regional Anesthesia and Pain Medicine Evidence-Based
Guidelines (Third Edition). Reg Anesth Pain Med 2010;35:64-101.
12. Ilfeld BM, Loland VJ, Mariano ER. Prepuncture ultrasound imaging to predict
transverse process and lumbar plexus depth for psoas compartment block and
perineural catheter insertion: a prospective, observational study. Anesth Analg
2010;110:1725-8.
13. Winnie AP, Ramamurthy S, Durrani Z, Radonjic R. Plexus blocks for lower
extremity surgery. Anesthesiol Rev 1974;1:1-6.
14. Chayen D, Nathan H, Chayen M. The psoas compartment block. Anesthesiology
1976;45:95-9.
10. Mannion S, O’Callaghan S, Walsh M, Murphy DB, Shorten GD. In with the new,
out with the old? Comparison of two approaches for psoas compartment block.
Anesth Analg 2005;101:259-64.
19
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American Society of Regional Anesthesia and Pain Medicine
2012
Use of Regional Anesthesia and Multi-Modal Pain Management in Reducing
Cancer Progression: Currently-Understood Basic Science Mechanisms
Julie H.Y. Huang, M.D., MBA
Chair-Elect, ASRA Resident Section Committee
Department of Anesthesiology and Critical Care
Medicine, Johns Hopkins Hospital
Baltimore, MD
Section Editor: Steven Orebaugh, M.D.
I
ncreasing evidence from pre-clinical data and largely
retrospective or population-based studies suggest the
importance of our role as anesthesiologists in the prevention
of cancer recurrence. As this outlook is tremendously exciting,
ongoing prospective clinical studies (http://clinicaltrials.gov)
are currently being undertaken to develop an evidence-based
approach to the perioperative care of these patients.
PERIOPERATIvE STRESS ANd ImmUNITY
Preclinical studies have shown that either overactivity or
underactivity of the surgical stress response after surgery, as well
as the systemic release of tumor cells during tissue manipulation,
influence cell-mediated immunity and long-term survival of
cancer patients. Recent studies suggest that tumor cells released
during surgery correlate with metastatic relapse potential.1 Tissue
injury releases a number of neuroendocrine and inflammatory
cytokines that suppress natural killer (NK) cytotoxic activity (our
body’s first-line defense mechanism against malignancy), foster
angiogenesis, and promote resistance to apoptosis. This cellular
environment in the perioperative period may be optimal for growth
of residual tumor cells and preexisting micrometastases while
promoting metastatic spread.2, 3 Suppressed NK cell activity has
been associated with higher morbidity and mortality for patients
with colorectal,4 gastric,5 lung,6 and head and neck cancers.7
Since the immune system is important to the prevention of
tumor growth, transient suppression of immune function in
the perioperative period may facilitate an increase in cancer
development and recurrence. Although surgery may result in
successful removal of the primary tumor, it also may facilitate
local cancer recurrence and metastases through a variety
of mechanisms (immunosupression, hypothermia, hypoxia,
adrenergic activation, pain, and need for blood transfusions).
Since our role as perioperative physicians and the anesthetics
20
2
we provide may influence cancer recurrence, understanding the
immediate and long-term consequences of different anesthetic
techniques is critical.
OPIOId ANd CANCER PROGRESSION
In addition to surgical stress, various anesthetic drugs and general
anesthesia have been reported to suppress NK cell activity in a
dose-dependent manner;8, 9 and the use of regional anesthesia
has been suggested to minimize tumor progression, although
in vivo and clinical evidence is currently limited. Mu (µ) opioid
receptor agonists are routinely given during the perioperative care
of cancer patients while cellular studies have shown their direct
effects on altering angiogenesis. Using several models of breast
cancer, melanoma, lung cancer, and squamous cell carcinoma,
investigators have demonstrated that exogenous (i.e., morphine)
and endogenous opioids (i.e., endorphin and endomorphins)
stimulate endothelial cell migration and proliferation.10, 10-16 In
addition to pro-angiogenesis, the µ-opioid receptor has been
implicated in regulating cancer progression and metastasis even
in the absence of exogenous opioids.17, 18 Opioids thus may
promote cancer recurrence in two ways: by affecting endothelial
barrier function directly, and by promoting neovascularization,
such that released tumor cells after surgery may invade
underlying tissues. While there are no controlled data in humans
to date, clinical trials are currently ongoing to determine the effect
of opioids on cancer progression and recurrence, angiogenesis,
immune function, and disease-free survival. Pre-clinical cellular
and animal studies implicate a potential therapeutic role of
µ-opioid receptor antagonists on cancer growth and metastasis,
and clinical trials are underway assessing the efficacy of
naltrexone as a possible adjuvant therapy in breast and brain
cancers.
EvIdENCE FOR mULTI-mOdAL PAIN mANAGEmENT
Chronic morphine use in a mouse model results in COX-2
overexpression in tumor cells, leading to increased prostaglandin
production and promoting angiogenesis, growth, and metastasis;
these effects are inhibited by celecoxib, a COX-2 inhibitor.19
Further, both selective and nonselective NSAIDs have been shown
to induce apoptosis and inhibit angiogenesis through direct effects
on endothelial cells.20 COX inhibitors are likely useful adjuncts in
cancer surgery, counterbalancing the negative effects of opioids,
including perioperative immunosuppression and pro-angiogenesis.
The blocking of the α-2 receptor has also been suggested as a
American Society of Regional Anesthesia and Pain Medicine
2012
Use of Regional Anesthesia and Multi-Modal Pain Management in Reducing
Cancer Progression: Currently-Understood Basic Science Mechanisms continued...
potential adjuvant therapy in cancer patients.21, 22 In addition,
β-blockers have been shown in mice with prostate carcinoma
to inhibit lumbar lymph node metastases through inhibition of
STAT-3 activity.23 Further, the combination of β-blockers and
COX-2 inhibitors in mice reduce the risk of tumor metastasis
after surgery with improved immune response.24
ANESThETIC AGENTS ANd CANCER
Preclinical studies have implicated several anesthetic agents as
having negative effects similar to opioids in cancer patients.8,
Ketamine, thiopental, and halothane in an animal model
reduce NK cell activity and promote tumor retention and
metastasis although the mechanism remains to be elucidated.30
Midazolam has been shown to decrease IL-8 levels, a
chemotactic and activating factor that is essential for neutrophil
adhesion and margination.31 Dexmedetomidine, an α-2 agonist,
was found in animal models to enhance tumor cell proliferation
and decrease cell apoptosis.21, 22 Propofol has been shown
conversely to exhibit protective effects through inhibition of
COX-2 and PGE2 and promotion of anti-tumor immunity.32, 33
The combination of propofol and remifentanil, compared to
isoflurane, as primary anesthetic in patients undergoing open
cholecystectomy, produces higher levels of anti-inflammatory
cytokine IL-10, which has been shown to have anti-tumor
activity.34 Another study demonstrates that patients undergoing
supratentorial tumor excision have improved surgical
stress-induced immune response with propofol compared
to isoflurane.35 In summary, based on preclinical studies,
inhalational anesthetics, ketamine, thiopental, midazolam,
dexmedetomidine, and opioids have been implicated in
facilitating cancer growth or recurrence while β-blockers,
tramadol, COX inhibitors, and propofol have been shown
to favorably reduce or inhibit tumor cell proliferation and
metastatic potential in vitro.
25-29
CURRENT CLINICAL EvIdENCE ANd FUTURE dIRECTIONS
Several hypothetical mechanisms support the perioperative use
of regional anesthesia and analgesia for patients undergoing
cancer surgery. Regional anesthesia with the use of local
anesthetic solutions attenuates the surgical stress response by
blocking afferent neural transmission, minimizes perioperative
immunosuppression, and reduces the overall use of opioid
and volatile anesthetics that have been shown to promote
cancer growth or recurrence in vitro. The sympathectomy
21
2
from regional anesthesia techniques may improve perfusion
and tissue oxygenation to the extremities while providing
superior perioperative analgesia. Although there are currently
no completed prospective clinical trials evaluating regional
anesthesia in reducing surgical stress and preserving immune
function, several preclinical and retrospective studies have
evaluated the association of regional anesthesia and reduced
risk of tumor progression and metastases in prostate,36-38
colorectal,39-44 cervical,45 ovarian,46, 47 and breast cancer
models.48-50
These studies suggest that complete regional anesthesia and/
or total IV anesthesia, instead of “standard” general anesthesia
(volatile anesthetics and intravenous opioids intraoperatively),
may provide protection against cancer recurrence or spread.
However, current clinical evidence based on retrospective study
designs has several limitations, including lack of randomization,
inherent potential for selection bias, and limited follow-up
duration. Several multi-center, prospective studies that are
underway should provide more definitive evidence-based
recommendations on the use of regional anesthesia and multimodal pain management in decreasing local or metastatic
cancer recurrence after surgery and improving patient
outcomes.
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analgesics on natural killer cell activity. AANA J. 77, 287-292 (2009).
9. Snyder, G. L. & Greenberg, S. Effect of anaesthetic technique and other
perioperative factors on cancer recurrence. Br. J. Anaesth. 105,
106-115 (2010).
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Use of Regional Anesthesia and Multi-Modal Pain Management in Reducing
Cancer Progression: Currently-Understood Basic Science Mechanisms continued...
10. Gupta, K. et al. Morphine stimulates angiogenesis by activating proangiogenic
and survival-promoting signaling and promotes breast tumor growth. Cancer
Res. 62, 4491-4498 (2002).
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Methylnaltrexone inhibits opiate and VEGF-induced angiogenesis: role of
receptor transactivation. Microvasc. Res. 72, 3-11 (2006).
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14. Boehncke, S. et al. Endogenous mu-opioid peptides modulate immune
response towards malignant melanoma. Exp. Dermatol. 20, 24-28 (2011).
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with 5-fluorouracil and bevacizumab on inhibition of vascular endothelial
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of mTOR inhibitors. J. Angiogenes Res. 2, 5 (2010).
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progression: a laboratory investigation. Anesth. Analg. 112, 558-567 (2011).
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progression: is there a direct effect? Anesthesiology 116, 940-945 (2012).
19. Farooqui, M. et al. COX-2 inhibitor celecoxib prevents chronic morphineinduced promotion of angiogenesis, tumour growth, metastasis and mortality,
without compromising analgesia. Br. J. Cancer 97, 1523-1531 (2007).
20. Jones, M. K. et al. Inhibition of angiogenesis by nonsteroidal anti-inflammatory
drugs: insight into mechanisms and implications for cancer growth and ulcer
healing. Nat. Med. 5, 1418-1423 (1999).
21. Bruzzone, A. et al. Alpha2-adrenoceptor action on cell proliferation and
mammary tumour growth in mice. Br. J. Pharmacol. 155, 494-504 (2008).
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mammary tumor growth acting through both the stroma and the tumor cells.
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23. Palm, D. et al. The norepinephrine-driven metastasis development of PC-3
human prostate cancer cells in BALB/c nude mice is inhibited by beta-blockers.
Int. J. Cancer 118, 2744-2749 (2006).
24. Benish, M. et al. Perioperative use of beta-blockers and COX-2 inhibitors may
improve immune competence and reduce the risk of tumor metastasis. Ann.
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25. Procopio, M. A. et al. The in vivo effects of general and epidural anesthesia on
human immune function. Anesth. Analg. 93, 460-5, 4th contents page (2001).
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and pain after surgery in cancer patients. Anesth. Analg. 90, 1411-1414 (2000).
27. Singleton, P. A. & Moss, J. Effect of perioperative opioids on cancer recurrence:
a hypothesis. Future Oncol. 6, 1237-1242 (2010).
28. Tavare, A. N., Perry, N. J., Benzonana, L. L., Takata, M. & Ma, D. Cancer
recurrence after surgery: direct and indirect effects of anesthetic agents. Int. J.
Cancer 130, 1237-1250 (2012).
32. Inada, T., Kubo, K., Kambara, T. & Shingu, K. Propofol inhibits cyclo-oxygenase
activity in human monocytic THP-1 cells. Can. J. Anaesth. 56, 222-229 (2009).
33. Kambara, T., Inada, T., Kubo, K. & Shingu, K. Propofol suppresses prostaglandin
E(2) production in human peripheral monocytes. Immunopharmacol.
Immunotoxicol. 31, 117-126 (2009).
34. Ke, J. J. et al. A comparison of the effect of total intravenous anaesthesia with
propofol and remifentanil and inhalational anaesthesia with isoflurane on the
release of pro- and anti-inflammatory cytokines in patients undergoing open
cholecystectomy. Anaesth. Intensive Care 36, 74-78 (2008).
35. Inada, T. et al. Effect of propofol and isoflurane anaesthesia on the immune
response to surgery. Anaesthesia 59, 954-959 (2004).
36. Biki, B. et al. Anesthetic technique for radical prostatectomy surgery affects
cancer recurrence: a retrospective analysis. Anesthesiology 109, 180-187
(2008).
37. Tsui, B. C. et al. Epidural anesthesia and cancer recurrence rates after radical
prostatectomy. Can. J. Anaesth. 57, 107-112 (2010).
38. Wuethrich, P. Y. et al. Potential influence of the anesthetic technique used
during open radical prostatectomy on prostate cancer-related outcome: a
retrospective study. Anesthesiology 113, 570-576 (2010).
39. Christopherson, R., James, K. E., Tableman, M., Marshall, P. & Johnson, F. E.
Long-term survival after colon cancer surgery: a variation associated with
choice of anesthesia. Anesth. Analg. 107, 325-332 (2008).
40. Gottschalk, A. et al. Association between epidural analgesia and cancer
recurrence after colorectal cancer surgery. Anesthesiology 113, 27-34 (2010).
41. Gupta, A., Bjornsson, A., Fredriksson, M., Hallbook, O. & Eintrei, C. Reduction
in mortality after epidural anaesthesia and analgesia in patients undergoing
rectal but not colonic cancer surgery: a retrospective analysis of data from 655
patients in central Sweden. Br. J. Anaesth. 107, 164-170 (2011).
42. Cummings, K. C.,3rd, Xu, F., Cummings, L. C. & Cooper, G. S. A comparison of
epidural analgesia and traditional pain management effects on survival and
cancer recurrence after colectomy: a population-based study. Anesthesiology
116, 797-806 (2012).
43. Day, A. et al. Retrospective analysis of the effect of postoperative analgesia
on survival in patients after laparoscopic resection of colorectal cancer. Br. J.
Anaesth. (2012).
44. Myles, P. S. et al. Perioperative epidural analgesia for major abdominal surgery
for cancer and recurrence-free survival: randomised trial. BMJ 342, d1491
(2011).
45. Ismail, H., Ho, K. M., Narayan, K. & Kondalsamy-Chennakesavan, S. Effect
of neuraxial anaesthesia on tumour progression in cervical cancer patients
treated with brachytherapy: a retrospective cohort study. Br. J. Anaesth. 105,
145-149 (2010).
46. de Oliveira, G. S.,Jr et al. Intraoperative neuraxial anesthesia but not
postoperative neuraxial analgesia is associated with increased relapse-free
survival in ovarian cancer patients after primary cytoreductive surgery. Reg.
Anesth. Pain Med. 36, 271-277 (2011).
47. Lin, L. et al. Anaesthetic technique may affect prognosis for ovarian serous
adenocarcinoma: a retrospective analysis. Br. J. Anaesth. 106, 814-822 (2011).
29. Gach, K., Wyrebska, A., Fichna, J. & Janecka, A. The role of morphine in
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221-230 (2011).
48. Exadaktylos, A. K., Buggy, D. J., Moriarty, D. C., Mascha, E. & Sessler, D. I. Can
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30. Melamed, R., Bar-Yosef, S., Shakhar, G., Shakhar, K. & Ben-Eliyahu, S.
Suppression of natural killer cell activity and promotion of tumor metastasis
by ketamine, thiopental, and halothane, but not by propofol: mediating
mechanisms and prophylactic measures. Anesth. Analg. 97, 1331-1339 (2003).
49. Deegan, C. A. et al. Effect of anaesthetic technique on oestrogen receptornegative breast cancer cell function in vitro. Br. J. Anaesth. 103, 685-690
(2009).
31. Galley, H. F., Dubbels, A. M. & Webster, N. R. The effect of midazolam and
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Analg. 86, 1289-1293 (1998).
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2
50. Sessler, D. I., Ben-Eliyahu, S., Mascha, E. J., Parat, M. O. & Buggy, D. J.
Can regional analgesia reduce the risk of recurrence after breast cancer?
Methodology of a multicenter randomized trial. Contemp. Clin. Trials 29, 517526 (2008).
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