American Society of Regional Anesthesia and Pain Medicine February 2018 - 27

ASRA Carl Koller Memorial Research Grant 2016: NMDA Antagonists and Steroids for the Prevention
of Persisting Postsurgical Pain After Thoracoscopic Surgeries: A Randomized Controlled, Factorial
Design, International, Multicenter Pilot Study
Study Acronym: Preventing pAIn with NMDA
antagonists-Steroids in Thoracoscopic
lObectomy Procedures (PAIN-STOP) Pilot Trial

T

he Carl Koller Memorial
Research Grant supports
research projects that
enhance patient care by
improving our understanding
and delivery of regional
analgesia and pain medicine
interventions. This research
funding goes a long way in
promoting research endeavors
from ASRA members within
North America. As a recipient
Harsha Shanthanna, MBBS, MD,
of this award for 2016, I would
MSc, FIPP, EDRA
like to express my sincere
Associate Professor, Department of
appreciation and gratitude for
Anesthesia, McMaster University
the ASRA research committee
Chronic Pain Physician,
and the Board of Directors. For
St. Joseph's Hospital
a clinician researcher like me,
Associate Chair, Research,
it is a great encouragement
Department of Anesthesia,
and motivation to continue
McMaster University
to engage in meaningful
Hamilton, Ontario, Canada
research work and bring value
to clinical care. As it is also
Section Editor: Kristopher Schroeder, MD
an acknowledgment of the
importance of our research
project, I would like to highlight its background, interventions, and
significance, apart from a study update as of September 2017.

BACKGROUND
Persistent postsurgical pain (PPSP),
which develops or increases after
a surgical procedure, affects
10-50% of the surgical population1
and has been recognized as a
health priority. Thoracic surgeries
have a high risk of PPSP,
affecting 25-60% of patients.2
Although video-assisted thoracic
surgery eliminates the need for
a rib-cutting incision, the risk of
clinically significant PPSP still
exists in 20-40% of patients.3 Because no effective modality of
prevention has been found, patients with PPSP continue to bear its
consequences.

and central sensitization.5 As central sensitization develops, pain
signaling enhancement leads to uncoupling of pain stimulus and
response (no stimulus or minimal stimulus can elicit a significant
pain response). Central to those changes are the release of
glutamate and its action on α-amino-3-hydroxy-5-methyl4-isoxazolepropionic acid and N-methyl-D-aspartate (NMDA)
receptors.5,6 Many of these changes can be potentially altered by
NMDA antagonists.7
Emerging evidence also supports the role of inflammatory-immune
cascades in the development of neuropathic pain, even in the
absence of a clinically observable nerve injury.8 Thoracic surgery
is major organ surgery and results in significant inflammatory
and immune responses.9 Corticosteroids can neutralize those
inflammatory-immune responses and hence modify the
development and perception of PPSP.10,11
STUDY INTERVENTIONS
Ketamine is a potent anesthetic and analgesic. It acts by blocking
NMDA receptors in a noncompetitive fashion. At low doses, it has
several perioperative benefits. At a dose of 1-6 μg/kg/min, it can
have antihyperalgesic effects without significant cardiovascular
and respiratory adverse effects.12 The psychomimetic adverse
effects are noted usually with a higher dose of ketamine (>2.5
μg/kg/min).13,14 A recent Cochrane review observed a small but
statistically important signal in its potential to decrease the
chances of PPSP, both at 3 and 6 months, when used for a duration
of more than 24 hours.15 However, parenteral administration of
ketamine is limited in some locations by the requirement for
increased or enhanced monitoring.
Memantine is a moderate-affinity, uncompetitive NMDA receptor
antagonist that blocks the sustained activation of the receptor
by glutamate that may occur
under pathologic conditions.
Memantine rapidly leaves the
NMDA receptor channel during
normal physiological activation.
It is 100% bioavailable after an
oral dose, undergoes minimal
metabolism, and exhibits a
terminal elimination half-life of
60-80 hours.16 Although it is
presently approved for use in
Alzheimer disease, its effects
on preventing pain have been
studied in both animal and human studies.17,18 However, most existing
studies are preliminary and small.

"The Carl Koller Memorial Research
Grant supports research projects
that enhance patient care by
improving our understanding and
delivery of regional analgesia and
pain medicine interventions."

Physical and emotional suffering can lead to chronic pain and
ultimately poor quality of life.4 Surgical injury results in peripheral

Steroids are potent anti-inflammatory agents and can affect
both inflammatory and immune pathways.11,19 Among commonly
used agents, dexamethasone is nearly five times as potent as

American Society of Regional Anesthesia and Pain Medicine
2018

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http://www.brightcopy.net/allen/asra/18-04
http://www.brightcopy.net/allen/asra/18-3
http://www.brightcopy.net/allen/asra/18-2
http://www.brightcopy.net/allen/asra/18-1
http://www.brightcopy.net/allen/asra/17-4
http://www.brightcopy.net/allen/asra/17-3
http://www.brightcopy.net/allen/asra/17-2
http://www.brightcopy.net/allen/asra/17-1
http://www.brightcopy.net/allen/asra/16-4
http://www.brightcopy.net/allen/asra/16-3
http://www.brightcopy.net/allen/asra/16-2
http://www.brightcopy.net/allen/asra/16-1
http://www.brightcopy.net/allen/asra/15-4
http://www.brightcopy.net/allen/asra/15-3
https://www.nxtbook.com/allen/asra/15-2
https://www.nxtbook.com/allen/asra/15-1
https://www.nxtbookmedia.com