E BRIEF REPORT

Effect of Intravenous Dexamethasone on the

Regression of Isobaric Bupivacaine Spinal Anesthesia:
A Randomized Controlled Trial
Juliane Guay, MD, Stephan R. Williams, MD, PhD, Florian Robin, MD, MSc, and
Monique Ruel, RN, CCRP

The effect of intravenous dexamethasone on the regression of sensory and motor block after
isobaric bupivacaine spinal anesthesia is unknown. We conducted a prospective, double-blind,
randomized controlled trial on 60 patients who received intravenously either placebo (group P)
or 8-mg dexamethasone (group D) during the intrathecal injection of 12-mg isobaric bupivacaine
0.5%. Primary outcome was the time from bupivacaine injection to regression of 2 dermatomes
in relation to the highest dermatome blocked by the spinal local anesthetic. Time to 2-derma-
tome regression was 85 minutes (74–96 minutes) in group P versus 87 minutes (76–98 min-
utes) in group D (P = .79).  (Anesth Analg XXX;XXX:00–00)

D
examethasone has been used for numerous years by
anesthesiologists to prevent postoperative nausea
and vomiting (PONV).1 More recently, in orthopedic
surgery, perioperative dexamethasone has been found to
decrease the need for postoperative opioids and the length
of hospitalization, without reported negative side effects.2,3
Dexamethasone is known to extend the duration of
peripheral nerve blocks when administered perineurally
and even intravenously (IV).4,5 However, the effect, if any,
of dexamethasone on the duration of isobaric bupivacaine
spinal anesthesia is unknown.
The primary aim of our study was to compare the effect
of IV 8-mg dexamethasone (D) versus placebo (P) on the
regression of isobaric bupivacaine spinal anesthesia,
defined as the time from bupivacaine injection to regres-
sion of 2 dermatomes in relation to the highest dermatome
blocked by the spinal local anesthetic (LA). Our hypothesis
was that dexamethasone would prolong the duration of
2-dermatome regression.
METHODS
This manuscript adheres to the applicable Consolidated
Standards of Reporting Trials (CONSORT) guidelines. This
study was approved by the institutional review board of the
Centre hospitalier de l’Université de Montréal, and written
informed consent was obtained from all subjects partici-
pating in the trial. The trial was registered before patient
enrollment at clinicaltrials.gov (NCT03078062; Principal
Investigator: S.R.W.; date of registration: March 3, 2017).
From the Département d’anesthésiologie, Centre hospitalier de l’Université
de Montréal, Hôpital Notre-Dame, Montréal, Québec, Canada.
Accepted for publication June 18, 2018.
Funding: Internal.
The authors declare no conflicts of interest.
Clinical Trials identifier: NCT03078062.
Protocol available at: www.clinicaltrials.gov/ct2/show/study/ NCT03078062.
Reprints will not be available from the authors.
Address correspondence to Stephan R. Williams, MD, PhD, Département
d’anesthésiologie, Centre Hospitalier de l’Université de Montréal, Hôpital
Notre-Dame, Montréal, QC H2L 4M1, Canada. Address e-mail to stephan.
williams@umontreal.ca.
Copyright © 2018 International Anesthesia Research Society
DOI: 10.1213/ANE.0000000000003670
Our study was a monocentric, prospective, double-
blind, randomized controlled trial.
Patients with American Society of Anesthesiologists score6
I–III, between 18 and 90 years of age, and undergoing lower
body surgery under isobaric bupivacaine spinal anesthesia
were recruited to participate. Patients with inability to provide
informed consent, history of allergy to amide LAs or dexa-
methasone, presence of a preexisting lower limb neurological
deficit, and chronic use of corticosteroids were not enrolled.
After placement of standard monitors and peripheral
IV access, patients received 0.5–2 mg IV midazolam as
needed. With aseptic technique, a 25-G pencil-point Pencan
(B. Braun, Mississauga, Ontario, Canada) needle was inserted
intrathecally at the L4-5 or L3-4 interspace, with the patient
in a seated position. Intrathecal positioning was confirmed
by observation of cerebrospinal fluid return through the nee-
dle. The isobaric bupivacaine was then injected. All patients
underwent spinal anesthesia with 12-mg isobaric bupiva-
caine 0.5%. Patients were randomly assigned to one of 2
groups according to a computer-generated list (randomi-
sation.com, seed 16137, blocks of 30–30). Beginning during
the intrathecal injection, patients in group D received 8-mg
dexamethasone IV in 500-mL normal saline (total, 502 mL),
while patients in group P received 502-mL normal saline IV
in 5–10 minutes, according to their allocation. Drugs used
for the study were prepared by an investigator not involved
with patient enrollment or data collection.
All patients underwent surgery in a supine position.
The level of sensory and motor blockade was evaluated
by a blinded investigator at 5, 10, 20, and 30 minutes after
injection of LA, then every 15 minutes until regression of 2
dermatomes in relation to the maximal level reached, and
then every 30 minutes afterward, before, during, and after
the surgery. Sensory block was evaluated with a Von Frey
6.1-g filament (Bioseb; North Coast Medical, Gilroy, CA)
and motor block with the Bromage scale.7
Propofol was administered intraoperatively (20–75 µg/
kg/min) to provide sedation/anxiolysis on an as-needed
basis while maintaining the ability to provide block-level
assessments.
At the end of surgery, patients were admitted to the postan-
esthesia care unit, where they received celecoxib 200 mg and

XXX 2018 • Volume XXX • Number XXX www.anesthesia-analgesia.org

1
Copyright © 2018 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
 EE Brief Report
acetaminophen 975 mg orally in the absence of contraindica-
tion. Analgesia was evaluated by a postanesthesia care unit
nurse according to a verbal numeric rating scale. Dosages of
0.2–0.4 mg IV hydromorphone were given every 5 minutes
if numeric rating scale was >3. In case of PONV, patients
received ondansetron 4 mg IV, dimenhydrinate 25–50 mg IV,
or haloperidol 0.5 mg IV as needed. Regression of sensory and
motor block, opioid consumption, and side effects was noted.
Primary outcome was regression of sensory block,
defined by time from injection of LA to 2-dermatome regres-
sion in relation to maximum dermatomal level reached.
Secondary outcomes included the following: maximum
sensory level, onset to maximal sensory level (time between
injection and maximum sensory level reached), total dura-
tion of sensory block (time between injection of LA and
complete regression of sensory block), total duration of
motor blockade (time between injection of LA and Bromage
0), time to first opioid, total opioid use over first 24 hours,
and adverse events (hypotension, bradycardia, PONV, uri-
nary retention, and headache). Data were collected from the
medical chart for inpatients, while outpatients were con-
tacted by phone 24 hours after surgery by an investigator
Enrollment
Assessed for eligibility (n=102)
Excluded (n=37)
Randomised (n=65)
Allocation
Allocated to Dexamethasone (n=32)
Allocated to Placebo (n=33)
Received allocated intervention (n=31)
Did not receive allocated intervention (n=1)
Unable to achieve spinal anesthesia
Follow-up
Discontinued intervention (n=3)
Discontinued intervention (n=1)
Non respect of research protocol
Sedation
Analysis
Analysed (n=30)
2   
www.anesthesia-analgesia.org
Copyright © 2018 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
unaware of group allocation to collect the previously men-
tioned data.
Statistical Analysis
We conducted a per-protocol analysis, and all data were
analyzed using Excel version 15.27 (Microsoft, Redmond,
WA) and SPSS 24 (SPSS, Chicago, IL). Normal distribution
of data was evaluated with the Shapiro-Wilk test. Normally
distributed continuous data were expressed as means and
standard deviations and were compared using unpaired,
2-sided, Student t tests. In case of nonnormal distribution,
continuous data were expressed as median and (minimum,
maximum) range values and were compared using Mann-
Whitney U tests. Fisher exact test (www.vassarstats.net)
was used to compare categorical data. P < .05 was consid-
ered statistically significant.
Considering a 2-dermatome regression mean time of 60 ±
30 minutes,8,9 an α error of .05, and a power (1 − β) of 0.8, to
detect a difference between groups of 22 minutes (smallest
difference considered clinically significant by the authors),
60 patients (30 patients per group) were required (https://
www.stat.ubc.ca/~rollin/stats/ssize/n2.html).
Not meeting inclusion criteria (n=7)
Declined spinal anesthesia (n=26)
Declined to participate (n=3)
Other reason (n=1)
Figure. CONSORT flow diagram. CONSORT
indicates Consolidated Standards of
Received allocated intervention (n=33)
Did not receive allocated intervention (n=0) Reporting Trials.
Non respect of research protocol
Sedation
Dose of bupivacaine
General anesthesia required
Analysed (n=30)
ANESTHESIA & ANALGESIA
 Intravenous Dexamethasone and Spinal Block Regression

RESULTS −0.78 to 4.78; P = .791). Similarly, there was no significant

Enrollment took place from May to October 2017. One difference regarding the time to total regression of sensory
hundred two patients were assessed for eligibility. Among and motor block. Maximum sensory level reached was the
them, 60 patients completed the study, 30 in each group same for both groups (T7). We did not find evidence for dif-
(Figure). Five patients were withdrawn after allocation for ference between groups in terms of postoperative analgesia
nonrespect of research protocol (wrong spinal dose [n = 1], and side effects (Table 2).
failed spinal anesthesia [n = 2], level of sedation that made
perioperative sensory block nonassessable [n = 2]). Their DISCUSSION
randomization numbers were blindly reassigned. This study demonstrated that IV 8-mg dexamethasone does
The 2 groups’ age, body mass index, gender, American not relevantly prolong sensory and motor block regression
Society of Anesthesiologists score, Apfel10 score, number after spinal anesthesia with isobaric bupivacaine. To our
of patients who required perioperative propofol sedation, knowledge, this study is the first to investigate the effects of
and type and duration of surgery are shown in Table 1. For IV dexamethasone on the duration of isobaric bupivacaine
our primary outcome, time to 2-dermatome regression, the spinal anesthesia in a general surgical population. This
difference between the 2 groups, was 2 minutes (95% CI, finding differs from the study of Shalu et al,11 in which the
authors demonstrated a prolongation of sensory block with
IV dexamethasone after spinal anesthesia with hyperbaric
Table 1.  Demographic Characteristics and Duration bupivacaine in an obstetrical population. This difference
of Surgery may be explained by differences in the baricity of bupiva-
Dexamethasone Placebo caine used, the study population, or the sensory block-level
Group (n = 30) Group (n = 30) evaluation methods. No difference in adverse events was
Age (y) 56 ± 18 58 ± 18 shown between the 2 groups. Although our study was not
BMI (kg/m2) 29 ± 6 30 ± 6
powered to detect observed differences in PONV, headache,
Gender
 Male 16 (53) 14 (47) and urinary retention, further study may be warranted
 Female 14 (47) 16 (53) (Table  2). The strengths of our study include clinical rel-
ASA score evance of 2-segment regression, innocuity of the interven-
 I 9 (30) 4 (13) tion, proper randomization, double-blinding, standardized
 II 16 (53) 20 (67) sensory stimuli, and complete evaluation data. In addition,
 III 5 (17) 6 (20)
concerning the evaluation of the primary outcome, when
Apfel score
 I 12 (40) 9 (30)
blocks on the left and right sides regressed asymmetri-
 II 13 (43) 15 (50) cally, we noted both sides separately in our database. We
 III 5 (17) 6 (20) analyzed the data using both shortest and longest times to
Type of surgery regression, and results were similar with both approaches.
 Orthopedic 26 (87) 23 (77) Only the values for the longest side to regress are presented.
 Urological/vascular/others 4 (13) 7 (23) Our study also had some limitations. First, heterogeneity
Duration of surgery (min) 83 ± 37 75 ± 24
in the types of surgery makes analgesia end points more
Perioperative propofol sedation 15 (50) 17 (57)
difficult to interpret but does not affect the primary end
Data are presented as mean ± SD or as a n (%).
point. Second, strict intention-to-treat was not followed
Abbreviations: ASA, American Society of Anesthesiologists; BMI, body mass
index. in our study because it was not clinically relevant: when

Table 2. Regression of Sensory and Motor Blocks, Analgesia, and Side Effects
Dexamethasone Placebo Effect Size
Group (n = 30) Group (n = 30) P Measure
Sensory block
  Highest sensory level T7 (T6, T8) T7 (T5, T8) .582 …
  2-dermatome regression (min) 87 (76–98) 85 (74–96) .791 2 (−0.78 to 4.78)
  Complete regression (min) 356 (336–375) 344 (323–365) .403 …
Motor block
  Regression to Bromage 0 (min) 298 (277–318) 274 (252–295) .101 …
Side effects, n (%) …
 Hypotension 5 (17) 3 (10) .712
 Bradycardia 5 (17) 5 (17) 1
 Nausea/vomiting 5 (17) 11 (37) .143
 Headache 0 (0) 3 (10) .237
  Urinary retentiona 7/26 (23) 2/23 (7) .145
Analgesia …
  Time to first analgesia (min) 510 (323–720) 420 (326–588) .303
  24-h opioid consumptionb (mg) 6.6 (3–10) 8.3 (5–20) .062
Data are presented as the median (interquartile range), mean (95% CI), or number of patients (%).
Abbreviation: CI, confidence interval.
a
Denominator adjusted to exclude patients (4 in group D and 7 in group P) who underwent urinary catheter insertion at the beginning of surgery, which made
assessment of urinary retention impossible.
b
Converted to parenteral morphine equivalent.

XXX 2018 • Volume XXX • Number XXX www.anesthesia-analgesia.org

3
Copyright © 2018 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
 EE Brief Report
spinal anesthesia cannot be performed or the patient cannot
respond to verbal questioning, it is not possible to assess
regression of block. Finally, patients undergoing total knee
arthroplasty had an adductor canal block performed for
postoperative pain control. Considering the limited sensory
territory affected by the adductor canal block, this limita-
tion never affected the evaluation of 2-segment regression
or total block regression. Finally, different clinicians per-
formed the spinal anesthesia; speed of injection was not
standardized. However, the effect of speed of injection on
the level of sensory block has not been demonstrated in pre-
viously published articles.12,13
In conclusion, there is no evidence that IV 8-mg dexa-
methasone prolongs sensory or motor block after isobaric
bupivacaine spinal anesthesia compared to placebo. Future
larger studies evaluating the effect of IV dexamethasone
combined with spinal anesthesia on analgesia, nausea/
vomiting, headache, and urinary retention would be of clin-
ical interest. E
DISCLOSURES
Name: Juliane Guay, MD.
Contribution: This author helped design and conduct the study,
analyze the data, and write the manuscript.
Name: Stephan R. Williams, MD, PhD.
Contribution: This author helped design and conduct the study,
analyze the data, and write the manuscript.
Name: Florian Robin, MD, MSc.
Contribution: This author helped design and conduct the study,
analyze the data, and write the manuscript.
Name: Monique Ruel, RN, CCRP.
Contribution: This author helped design and conduct the study,
analyze the data, and write the manuscript.
This manuscript was handled by: Richard Brull, MD, FRCPC.
REFERENCES
1. Henzi I, Walder B, Tramèr MR. Dexamethasone for the preven-
tion of postoperative nausea and vomiting: a quantitative sys-
tematic review. Anesth Analg. 2000;90:186–194.
4   
www.anesthesia-analgesia.org
Copyright © 2018 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
2. Waldron NH, Jones CA, Gan TJ, Allen TK, Habib AS. Impact of
perioperative dexamethasone on postoperative analgesia and
side-effects: systematic review and meta-analysis. Br J Anaesth.
2013;110:191–200.
3. De Oliveira GS Jr, Almeida MD, Benzon HT, McCarthy RJ.
Perioperative single dose systemic dexamethasone for postop-
erative pain: a meta-analysis of randomized controlled trials.
Anesthesiology. 2011;115:575–588.
4. Albrecht E, Kern C, Kirkham KR. A systematic review and
meta-analysis of perineural dexamethasone for peripheral
nerve blocks. Anaesthesia. 2015;70:71–83.
5. Chalifoux F, Colin F, St-Pierre P, Godin N, Brulotte V. Low dose
intravenous dexamethasone (4 mg and 10 mg) significantly pro-
longs the analgesic duration of single-shot interscalene block
after arthroscopic shoulder surgery: a prospective randomized
placebo-controlled study. Can J Anaesth. 2017;64:280–289.
6. Sathiyakumar V, Molina CS, Thakore RV, Obremskey WT, Sethi
MK. ASA score as a predictor of 30-day perioperative readmis-
sion in patients with orthopaedic trauma injuries: an NSQIP
analysis. J Orthop Trauma. 2015;29:e127–e132.
7. Bromage PR. A comparison of the hydrochloride and carbon
dioxide salts of lidocaine and prilocaine in epidural analgesia.
Acta Anaesthesiol Scand Suppl. 1965;16:55–69.
8. Sheskey MC, Rocco AG, Bizzarri-Schmid M, Francis DM,
Edstrom H, Covino BG. A dose-response study of bupivacaine
for spinal anesthesia. Anesth Analg. 1983;62:931–935.
9. Kallio H, Snäll EV, Kero MP, Rosenberg PH. A comparison of
intrathecal plain solutions containing ropivacaine 20 or 15 mg
versus bupivacaine 10 mg. Anesth Analg. 2004;99:713–717.
10. Weilbach C, Rahe-Meyer N, Raymondos K, Weissig A,
Scheinichen D, Piepenbrock S. Postoperative nausea and
vomiting (PONV): usefulness of the Apfel-score for identifi-
cation of high risk patients for PONV. Acta Anaesthesiol Belg.
2006;57:361–363.
11. Shalu PS, Ghodki PS. To study the efficacy of intravenous dexa-
methasone in prolonging the duration of spinal anesthesia in
elective cesarean section. Anesth Essays Res. 2017;11:321–325.
12. Bucx MJ, Kroon JW, Stienstra R. Effect of speed of injection
on the maximum sensory level for spinal anesthesia using
plain bupivacaine 0.5% at room temperature. Reg Anesth.
1993;18:103–105.
13. Stienstra R, Van Poorten F. Speed of injection does not affect
subarachnoid distribution of plain bupivacaine 0.5%. Reg
Anesth. 1990;15:6–11.
ANESTHESIA & ANALGESIA