2. 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
3. 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).
4. 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).
5. 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).
6. 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
7. 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
8. 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!!
10. 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
11. 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).
12. 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).
13. 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
14. RANDOMIZED, CONTROLLED, DOUBLE-BLIND
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.
15. RANDOMIZED, CONTROLLED, DOUBLE-BLIND
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.
16. 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.
17. 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.
19. 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.
21. 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).
22. 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).
23. PROPOSED MECHANISM FOR RAPID ACTION
G-protein mediated
retrograde
endocannabinoid
suppression of
presynaptic
glutamate (Tasker, 2005).
24. 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
25. 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).
26. 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
27. 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)
28. 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.
29. 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.
30. 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.
