decadron powerpoint- final copy

DEXAMETHASONE (DECADRON):
An examination of single dose decadron: the basic
pharmacodynamics and role as an adjuvant to regional
anesthesia.
By
Devon Boyd NAR

OBJECTIVES
 Briefly discuss:
 The mechanism of action of corticosteroids --
specifically decadron.
 Current uses
 Antiemetic
 Anti-inflammatory
 Discuss new revelations about how decadron can
enhance our anesthetics.
 Explore the use of decadron as an adjuvant to
regional anesthesia.
 Decrease block onset time
 Double the length of motor block
 Double the length of analgesia

DECADRON AS AN ANTIEMETIC
 Decadron’s role as an
antiemetic is related to
its ability to reduce the
cellular production of
serotonin (5-HT3)
through the inhibition of
the production of
tryptophan
hydroxylase the
enzyme that converts
tryptophan to serotonin
(Allen, 2007).

DECADRON AS AN ANTIEMETIC
 5-HT3 released from the gut during surgery is a
contributor to postoperative nausea and vomiting.
 When given in combination with Zofran, a
(5-HT3) receptor antagonist, this
combination is highly effective against
nausea (Allen,2007).

GENERAL STATEMENTS ABOUT DECADRON
 Decadron is a synthetic glucocorticoid with minimal
mineralocorticoid activity.
 Single dose – no disruption of the patient’s electrolyte or
fluid balance (Allen, 2007).
 Potent anti-inflammatory
 25-50 times the potency of hydrocortisone
 16 times the potency of prednisone (Allen, 2007).

WHAT IS THE PROVEN MECHANISM OF ACTION
OF DECADRON?
 Glucocorticoid-receptor
complexes cross the
nuclear membrane and
modulates gene mediated
protein production (Tasker,
2005).
 This requires 45 min – 1
hour for full effect
 This is why decadron is
more effective at treating
nausea if it is given right
after induction of general
anesthesia

CELL NUCLEUS GENE MODULATION -- ROLE IN
REDUCTION OF INFLAMMATORY AND CHEMOTAXIC
MEDIATORS
 Decreased production of proteins includes the decreased production of:
 Bradykinin
 Decreases both the cell mRNA expression and the response to Bradykinin binding
 COX-2
 Prostaglandin
 Tryptophan Hydroxylase
 Serotonin (5-HT3)
 Interlukin-1
 Interlukin-2
 Interlukin-6 (Allen, 2007)
 Substance P
 Nitric oxide
 Tumor Necrosis Factor
 Indirectly histamine release
 Histamine is released from mast cells in response to
 Substance p
 Kinins
 Interlukin-1 (Kelly, 2001)
 The effect of this steroid is to reduce the production of excitatory
neurotransmitters.
 Reduction of the above chemical mediators is very important

MECHANISM OF ACTION OF DECADRON
CONTINUED
 Binding of decadron to cellular DNA results in changes
in metabolism of:
 Carbohydrates
 Increases gluconeogenesis
 Increases blood glucose levels (Allen,2007).
 Fats
 Corticosteroids increase the production of HMG CoA
 Allows cells to make more of their own cholesterol
 Increases circulation of Low Density Lipoproteins (LDL)
 Chronic use results in:
 Increased serum cholesterol
 Deposition of fat
 Results in Cushing’s Syndrome with chronic use (Allen,2007)
 Proteins
 Decreases the production of proteins (Allen, 2007)
• This is one of the BIG features of interest in the perioperative
and postoperative setting!!

REDUCESTHECHEMICALSTHATMEDIATEPAIN
This illustration
represents a C-
fiber
nociceptor.
The production
of these
mediators is
inhibited by
decadron.
These are the
chemicals
responsible for
“wind-up” pain.
 C Fiber Nociceptor

EFFECT ON POSTOPERATIVE PAIN --- SINGLE
PREOPERATIVE OR PERIOPERATIVE DOSE OF
DECADRON TO A GENERAL SURGERY PATIENT
 Two meta-analysis’ conducted by De Oliviera et al.
(2011) and Waldron et al. (2013) suggest that
decadron can:
 Modestly decrease postoperative opioid requirements
for patients having open abdominal surgery:
 16.8% during the first 24 hours
 De Oliviera et al. showed a statistically significant
decrease in time to discharge:
 5.5 hour on average

THE MOST BANG FOR THE BUCK
 The suggested dose of
single dose decadron is
0.1-0.2 mg/kg with a
plateau effect at doses
>10mg (De Oliveira, 2011).
 This dose is effective as
an antiemetic while also
being effective at
reducing pro-
inflammatory and pain
inducing proteins (Allen, 2007).

AS AN ADJUVANT FOR REGIONAL ANESTHESIA
 Preservative free
decadron 8mg-10mg
administered as an
adjuvant to local
anesthetic for neuraxial
and peripheral nerve
blocks dramatically
increases the length of
analgesia (by 100% to
180%)(Cummings III, 2011).
 It is safe for use in both
neuraxial and peripheral
nerve blocks (cummings III, 2011).

RANDOMIZED, CONTROLLED, DOUBLE-BLIND
TEST RESULTS
 This is from the British Journal of Anesthesia June
2011
 K.C. Cummings III et al.
 Researchers sought to determine the effect of
adding 8ml of preservative free decadron to 0.5%
Bupivacaine and 0.5% Ropivacaine used for
interscalene blocks
 Results:
 Length of analgesia
 Plain 0.5% Ropivacaine -- 11.8 hours
 0.5% Ropivacaine with 8mg decadron -- 22.2 hours
 Plain 0.5% Bupivacaine-- 14.8 hours
 0.5% Bupivacaine with 8mg decadron-- 22.4 hours

TEST RESULTS CONTINUED
 This is from the Indian Journal of Anesthesia April 2013
 P.A Biradar et al.
 Researchers sought to determine the effect of the
addition of 8mg of preservative free decadron to 1.5%
lidocaine (7mg/kg) with epinephrine (1:200,000)to a
supraclavicular brachial plexus block.
 Results
 Onset of sensory blockade:
 Lido ĉ Epi. – 16.0 + 2.3 min.
 Lido ĉ Epi and 8mg decadron – 13.4 + 2.8 min.
 Onset of motor blockade
 Lido ĉ Epi – 18.7 + 2.8 min.
 Lido ĉ Epi and 8mg decadron – 16.0 + 2.7 min.
 Duration of sensory blockade
 Lido ĉ Epi – 159 + 20.1 Min
 Lido ĉ and 8mg decadron – 326 + 58.6 min.
 Duration of motor block
 Lido ĉ Epi. – 135.5 + 20.3 min.
 Lido ĉ and 8mg decadron – 290.6 + 52.7 min.

TEST RESULTS CONTINUED
 This is from the Saudi
Journal of Anesthesia
2011
 Bani-hashem et al.
 Sought to determine
the effect of the
addition of 8mg of
decadron to a 0.5%
bupivacaine spinal.

YOU CAN GIVE DECADRON I.V. WITH THE
SAME EFFECT
 New research shows that
I.V. decadron
administered 45min-
1hour before regional
anesthesia has the same
analgesia extending
effect as decadron
administered perineurally
(Desmet, 2013)!
 To avoid perineal itching
administer in 50ml-100ml
0.9% NaCl over 10
minutes.

TWO RANDOMIZED, CONTROLLED, AND DOUBLE-
BLINDED TRIALS SUGGEST THAT I.V. DECADRON
CAN HAVE THE SAME EFFECT AS PERINEURALLY
ADMINISTERED DECADRON
 Egyptian Journal of
Anesthesia March 2011
 Abdelmonem et al.
 Sought to determine if
perianal injection of 0.5%
bupivacaine and
decadron was equivalent
to perianal injection of
0.5%bupivacaine after
I.V. decadron 8mg for
hemorrhoidectomy
patients.

RESULTS FROM ABDELMON ET AL.
 Onset of sensory blockade:
 0.5% bupivacaine 20ml alone – 5.5 + 1.2 minutes
 0.5% bupivacaine 20ml ĉ 8mg decadron -- 3.8 + 0.7 minutes
 0.5% bupivacaine 20ml ĉ 8mg I.V. decadron-- 3.8 + 0.9 minutes
 Onset of motor blockade:
 0.5% bupivacaine 20ml ĉ 8mg decadron -- 4.0 + 0.7 minutes
 Duration of analgesia:
 0.5% bupivacaine 20ml ĉ 8mg decadron – 287.7 + 21.0 minutes

I.V. DECADRON CAN HAVE THE SAME EFFECT AS
PERINEURALLY ADMINISTERED DECADRON
 British Journal of
Anesthesia April 2013
 Desmet et al.
 Sought to determine if
0.5% ropivacaine with
decadron 10mg
injected to perform an
interscalene nerve
block was equivalent to
0.5% ropivacaine
injected interscalene
after an I.V. infusion of
decadron 10mg.

RESULTS FROM DESMET ET AL.
 Length of analgesia:
 0.5% bupivacaine alone – 757 minutes
 0.5% bupivacaine ĉ 10mg decadron -- 1405 minutes
 0.5% bupivacaine ĉ 10mg I.V. decadron-- 1275 minutes
 Increase in postoperative blood glucose:
 0.5% bupivacaine alone – 0 mg / dl
 0.5% bupivacaine ĉ 10mg decadron -- 38 mg / dl
 0.5% bupivacaine ĉ 10mg I.V. decadron-- 51 mg / dl

RAPID ACTION SEEN WITH PERINEURAL
INJECTION
 There is a decrease in
onset time of regional
anesthesia when
decadron is used as an
adjuvant to local
anesthetics.
 This cannot be explained
through the known action
of glucocorticoids.
 The fact is – there is not
a definitive explanation
for why decadron
decreases the onset time
of regional anesthesia
(Abdelmonem, 2011).

RAPID ACTION SEEN WITH PERINEURAL
INJECTION
 There are many proposed mechanisms of
immediate action of decadron
 Upregulation of K+ channels leading to neural
hyperpolarization of C fibers (Attardi, 1993).
 Intraneural acidification - leading to increased and
sustained ionization of local anesthetic (Kapacz, 2003).
 Vasoconstriction – reducing local anesthetic absorption
(Kapacz, 2003).
 G-protein mediated retrograde endocannabinoid
suppression of presynaptic glutamate (Tasker, 2005).

PROPOSED MECHANISM FOR RAPID ACTION
 G-protein mediated
retrograde
endocannabinoid
suppression of
presynaptic
glutamate (Tasker, 2005).

EFFECT OF A SINGLE DOSE OF DECADRON ON
BLOOD GLUCOSE
 Desmet et al. 2013
 Decadron perineural
injection 10mg
 Caused patient blood
glucose to rise by a mean
of 38mg/dl for 24 hours
 Decadron I.V. injection
10mg
 Caused patient blood
glucose to rise by 51
mg/dl for 24 hours

EFFECT OF A SINGLE DOSE OF DECADRON ON
WOUND HEALING
 A single dose of IV decadron is out of the
circulatory system within 3 hours (Allen, 2007).
 The single dose is completely metabolized within
24 hours (Allen, 2007).
 There is no difference in wound healing at two
week and six week intervals between decadron and
a control group (De Oliviera, 2011).

WHY IS IT SAFE TO INJECT DECADRON INTO
THE NEURAXIAL SPACE
 Decadron is frequently
used as an anti-
inflammatory in pain
control
 Metabolized and
excreted within 24
hours
 Not an ester
 Does not have to
undergo ester
hydrolysis in order to be
metabolized

DECADRON AS AN ADJUVANT TO REGIONAL
ANESTHETICS, INCLUDING SPINALS AND EPIDURALS
 Particulate size of
corticosteroids commonly
injected in the neuraxial
space:
 Methylprednisolone –Large
particulate size
 Betamethasone – Medium
particulate size
 Dexamethasone – no
particulates
 No potential for embolic
infarction after particulate
corticosteroid injection into
an arterial vessel
(MacMahon, 2009)

REFERENCES
 Abdelmonem, A., & Rizk, S. (2011). Comparative study between
intravenous and local dexamethasone as adjuvant to
bupivacaine in perianal block. Egyptian Journal of
Anesthesia, 27, 163-168.
 Allen, K. (2007). Dexamethasone: an all purpose agent? Australian
Anaesthesia, 65-70.
 Attardi, B., Takimoto, K., Grealy, R., Severns, C., & Levatitan, E.
(1993). Glucocorticoid induced up-regulation of a pituitary K+
channel mRNA in vitro and in vivo. Receptors Channels, 1, 287-
293.
 Bani-hashem, N., Hassan-nasab, B., & Jabbari, A. (2011, October-
December). Addition of intrathecal dexamethasone to
bupivacaine for spinal anesthesia in orthopedic surgery. Saudi
journal of anesthesia, 5(4), 382-386.
 Biradar, P., Kaimar, P., & Gopalakrishna, K. (2013). Effect of
dexamethasone added to lidocaine in supraclavicular brachial
plexus block: a prospective, randomised, double-blind study.
Indian Journal of Anesthesia, 57(2), 180-184.
 Chapman, R., Tuckett, R., & Song, C. (2008). Pain and stress in a
systems perspective: reciprocal neural, endocrine and immune
interactions. Journal of Pain, 9(2), 122-145.

REFERENCES CONTINUED
 Cummings III, K., Napierkowski, D., Parra-Sanchez, I., Kurz, A.,
Dalton, J., Brems, J., & Sessler, D. (2011). Effect of
dexamethasone on the duration of interscalene nerve blocks
with ropivacaine or bupivacaine. British Journal of
Anesthesia, 107(3), 446-453.
 De Oliveira, G., Almeida, M., Benzon, H., & McCarthy, R. (2011).
Perioperative single dose systemic dexamethasone for
postoperative pain. Anesthesiology, 115(3), 575-588.
 Desmet, M., Braems, H., Reynvoet, M., Plasschaert, S., Van
Cauwelaert, J., Pottel, H., . . . Van de Velde, M. (2013). I.V. and
perineural dexamethasone are equivalent in increasing the
analgesic duration of a single-shot interscalene block with
ropivacaine for shoulder surgery: a prospective, randomized,
placebo-controlled study. British Journal of Anesthesia, 1-8.
 Elston, M., Conaglen, H., Hughes, C., Tametea , J., Meyer-Rochow,
G., & Conaglen, J. (2013). Duration ofcortisol suppression
following a single dose of dexamethasone in healthy
volunteers: a randomised double-blind placebo-controlled
trial. Anesthesia Intensive Care, 41(5), 596-601.

REFERENCES CONTINUED
 Islam, S., Hossain, M., & Maruf, A. (2011). Effect of addition of
dexamethasone to local anesthetics in supraclavicular brachial
plexus block. JAFMC Bangladesh, 7(1), 11-14.
 Kapacz, D., Lacouture, P., Wu, D., Nandy, P., Swanton, R., & Landau,
C. (2003). The dose response and effects of dexamethasone
on bupivacaine microcapsules for intercostal blockade (T9 to
T11) in healthy volunteers. Anesthesia and Analgesia, 96, 576-
582.
 Kelly, D., & Ahmad, M. (2001). Preemptive analgesia I: physiological
pathways and pharmacological modalities. Canadian J ournal
of Anesthesia, 1000-1010.
 Tasker, J., Di, S., & Malcher-Loez, R. (2005). Rapid Central
Corticosteroid Effects: Evidence for Membrane Glucocorticoid
Receptors in the Brain. Integrative and Comparative Biology,
45(4), 665-671.
 Ullian, M. (1999). The role of corticosteroids in the regulation of
vascular tone. Cardiovascular Research, 41, 55-64.
 Waldron, N., Jones, C., Gan, T., Allen, T., & Habib, A. (2013). Impact
of perioperative dexamethasone on postoperative
analgesia and side-effects. British Journal of Anesthesia, 1(2),
191-200.

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