International Journal of Obstetric Anesthesia (2020) 44, 116–121

0959-289X/$ - see front matter Ó 2020 Elsevier Ltd. All rights reserved.
https://doi.org/10.1016/j.ijoa.2020.08.009

SHORT REPORT
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Intra-operative ketorolac 15 mg versus 30 mg for analgesia

following cesarean delivery: a retrospective study
M. Yurashevich, C. Pedro, M. Fuller, A.S. Habib
Department of Anesthesiology, Duke University School of Medicine, Durham, NC, USA

ABSTRACT
Background: Ketorolac is a nonsteroidal anti-inflammatory drug used as part of multimodal analgesia in women undergoing
cesarean delivery. The lowest effective dose of ketorolac that best optimizes analgesia without increasing side effects is unclear.
We performed this retrospective study to compare the analgesic efficacy of 15 mg or 30 mg ketorolac administered intra-
operatively to our obstetric population.
Methods: We included patients who underwent cesarean delivery under neuraxial anesthesia and received 15 mg or 30 mg of
ketorolac intra-operatively. Our multimodal analgesic regimen is standardized and includes 150 mg spinal or 3 mg epidural mor-
phine, 975 mg rectal acetaminophen, and 15–30 mg intravenous ketorolac within 15 min of surgery completion. The primary out-
come was opioid use in the first 6 h after surgery. Secondary outcomes were opioid use at 24 and 48 h, opioid dose, pain scores,
breastfeeding, postoperative serum creatinine and need for rescue anti-emetics.
Results: One-thousand-three-hundred and forty-nine patients were analyzed (15 mg ketorolac n=999; 30 mg n=350). There was
no difference between the two groups in patient demographics or intra-operative characteristics. There was no significant differ-
ence between groups for opioid use at 6 h after surgery (50.3% vs 52.0%, odds ratio [95% confidence interval] 1.13 [0.87 to 1.47]).
There were also no significant differences between the groups for secondary outcomes.
Conclusions: There was no difference in opioid use between patients receiving either a 15 mg or a 30 mg dose of ketorolac given
intra-operatively for postoperative analgesia following cesarean delivery.
Ó 2020 Elsevier Ltd. All rights reserved.

Keywords: Ketorolac; Dose; Cesarean delivery; Analgesia

Introduction
In the USA, ketorolac is widely used for pain manage-
ment following cesarean delivery. The lowest effective
dose that maximizes analgesia without increasing side
effects is unclear. The manufacturer’s recommended
intravenous (IV) dose is 30 mg for adults <65 years of
age.1 A lower dose, for example 15 mg, is used in the
general surgical population, but there are no data com-
paring the analgesic efficacy or impact on breastfeeding
success of lower versus higher doses in women undergo-
ing cesarean delivery under neuraxial anesthesia. Since
both doses were used in our institutional practice as part
of a standardized protocol for post-cesarean analgesia,
we performed this retrospective analysis to compare
the analgesic efficacy after both doses. We hypothesized
that opioid use would be lower with the 30 mg dose.
Accepted August 2020
Correspondence to: A.S. Habib, Department of Anesthesiology, Duke
University School of Medicine, 2301 Erwin Road, Box 3094, Mail Sort
9, Durham, NC 27710, USA.
E-mail address: ashraf.habib@duke.edu
Methods
Duke University Institutional Review Board approved
this retrospective analysis. We included patients who
underwent cesarean delivery between January 1, 2016
and August 22, 2017. Patients who received general
anesthesia, were <18 years old, or who had a history
of chronic opioid use, were excluded. Data were
retrieved from our electronic medical record (EPIC,
Verona, WI). In January 2016, we instituted a standard-
ized multimodal analgesic protocol for cesarean deliv-
ery. Intra-operatively, patients received neuraxial
morphine 150 mg intrathecally or 3 mg epidurally, and
975 mg acetaminophen per rectum (PR) with 15 or
30 mg of IV ketorolac administered within 15 min of
the completion of surgery. Vials containing both doses
of ketorolac were available at a comparable cost (US$
0.95 and US$ 1.25). The choice of dose was at the discre-
tion of the anesthesiologist who supervises an anesthesia
provider (resident, fellow or a certified registered nurse
anesthetist) for all cases. Postoperatively, patients
M. Yurashevich et al. 117

received acetaminophen 975 mg per os (PO) every 6 h,
and ketorolac 15 mg IV every 6 h for three doses, fol-
lowed by ibuprofen 600 mg PO every 6 h. Breakthrough
pain was managed with PO oxycodone on demand
according to the verbal numerical pain score (0=no
pain, 10=worst possible pain), where 5 mg was given
for pain scores 4–6 and 10 mg for pain scores 7–10. Pain
scores are recorded on admission to and at discharge
from the post-anesthesia care unit, and subsequently
four hourly and within one hour of administration of
opioid. Intravenous fentanyl and hydromorphone were
available for pain inadequately relieved by oxycodone.
Anti-emetic prophylaxis was not standardized during
the duration of the study.
The primary outcome was opioid use in the first 6 h
after surgery (the elimination half-life of ketorolac is
5–6 h).1 Secondary outcomes included opioid use at 24
and 48 h, opioid dose in oxycodone mg equivalents
(OME)2 at 6, 24 and 48 h, the average and maximum
pain score at 6 h, the number of patients with serum cre-
atinine levels >0.9 mg/dL, the number who breastfed
within 48 h after surgery, and the use of rescue anti-
emetics over the first 48 h. An a priori power analysis
assuming 50% opioid use within 6 h in the 15 mg ketoro-
lac group and 40% in the 30 mg group determined that a
sample size of 1 350, in a 1000:350 ratio, provided 90%
power to detect a difference.
Descriptive statistics were generated within each dose
group and presented as number (percentage) and med-
ian (IQR) for categorical and continuous variables,
respectively. Baseline characteristics and intra-
operative variables were compared between the two

Table 1 Patient demographics and intra-operative variables

Ketorolac 15 mg Ketorolac 30 mg P-value
(n=999) (n=350)
Age (y) 30 (26, 35) 31 (26, 35) 0.786
BMI (kg/m2) 33.1 (28.6, 39.5) 33.7 (29.3, 40.0) 0.235
Gestational age (weeks) 39 (37, 39) 39 (37, 39) 0.417
Parity 0.162
multiparous 776 (77.7%) 285 (81.4%)
primiparous 223 (22.3%) 65 (18.6%)
Race 0.297
African-American 347 (34.7%) 124 (35.4%)
Asian 86 (8.6%) 19 (5.4%)
Caucasian 351 (35.1%) 129 (36.9%)
Other 215 (21.5%) 78 (22.3%)
Pre-eclampsia 70 (7%) 21 (6%) 0.601
Neuraxial technique 0.166
epidural 471 (47.2%) 150 (42.9%)
spinal or CSE 528 (52.9%) 200 (57.1%)
Cesarean priority 0.053
scheduled 344 (34.5%) 148 (42.5%)
unscheduled 522 (52.4%) 163 (46.8%)
urgent 104 (10.4%) 31 (8.9%)
emergency 27 (2.7%) 6 (1.7%)
Repeat cesarean delivery 400 (40.0%) 142 (40.6%) 0.912
Surgical duration (min) 62 (52, 74) 60 (52, 71) 0.151
Estimated blood loss (mL) 800 (700, 850) 800 (700, 800) 0.518
Attending anesthesiologist <0.001
A 78 11
B 114 35
C 103 48
D 51 94
E 71 41
F 110 16
G 77 24
H 119 23
I 48 17
J 150 28
K 78 13
Data are number (%) or median (interquartile range).BMI: body mass index. CSE: combined spinal-epidural.Missing data for BMI: 18 missing in
15 mg group and 7 in 30 mg group.Missing data for cesarean priority: two missing in 15 mg group and two in 30 mg group.Missing data for
surgical duration: 52 missing in 15 mg group and 12 in 30 mg group. A-J include obstetric anesthesiologists in practice for 1–20 years post-
fellowship training. K includes four general anesthesiologists who only participate in out-of-hours shifts.
118 Intra-operative ketorolac 15 mg versus 30 mg for analgesia following cesarean delivery: a retrospective study
groups and between patients who received, versus those
who did not receive, ketorolac using chi-squared and
Wilcoxon Rank-Sum tests as appropriate. Continuous
outcome variables and binary outcomes were compared
between groups using linear regression and logistic
regression models, respectively. Postoperative anti-
emetic use was compared using a proportional odds
logistic regression model. We adjusted for baseline char-
acteristics and intra-operative variables with P <0.1 in
the regression models (Table 1). Results of these models
are presented as adjusted mean differences (continuous
outcomes) or odds ratios (OR) (categorical outcomes)
with 95% confidence intervals (CIs). Since the choice
of the dose of ketorolac was at the discretion of the
attending anesthesiologist, we performed a Fisher’s
exact test to assess if physician preference was an impor-
tant factor in dose selection. We also performed a mixed
logistic regression model with a random intercept for
anesthesiologist to assess if the number of years in prac-
tice or obstetric anesthesia fellowship training were asso-
ciated with dose selection. We compared opioid use,
opioid dose and postoperative pain scores between those
who received versus those who did not receive ketorolac
using chi-squared and Wilcoxon Rank-Sum tests. Statis-
tical analysis was conducted using SAS, version 9.4
Fig. 1 Flow diagram of patient selection. Other locations: another hospital within the Duke Health System. DUH OB OR: Duke
University Hospital Obstetric Operating Room
(SAS Institute, Cary NC) and R version 3.5.3 (http://
www.r-project.org).
Results
Two-thousand-seven-hundred and seven patients under-
went cesarean delivery during our study period. One-
thousand-three-hundred and forty-nine patients met
our inclusion criteria (Fig. 1); 999 patients received
15 mg of ketorolac and 350 patients received 30 mg.
Compared with patients who received ketorolac, those
who did not receive ketorolac (n=325) were younger
and at a lower gestational age, had a higher rate of
pre-eclampsia and a larger intra-operative estimated
blood loss, reported higher pain scores and consumed
more opioids postoperatively (Supplemental Table).
There were no statistically significant differences
between the two ketorolac dose groups with respect to
patient demographics or intra-operative characteristics
(Table 1). A Fisher’s exact test comparing dose selection
across attending anesthesiologists found a highly signif-
icant (P <0.0001) effect of physician on the dose
received. However, neither years in practice (OR, 95%
CI 1.05, 0.99 to 1.12 per year, P=0.085) nor fellowship
training (OR, 95% CI 1.11, 0.50 to 2.43, P=0.803) were
 M. Yurashevich et al.
Table 2 Opioid use and dose, anti-emetic use, incidence of breastfeeding, pain scores and postoperative creatinine values
Ketorolac 15 mg Ketorolac 30 mg Odds ratio or adjusted mean difference P-value
(n=999) (n=350) [95% confidence interval]
Opioid use at 6 h 502 (50.3%) 182 (52.0%) 1.13 [0.87 to 1.47] 0.361
Opioid use at 24 h 717 (71.8%) 265 (75.7%) 1.31 [0.96 to 1.77] 0.084
Opioid use at 48 h 863 (86.4%) 311 (88.9%) 1.21 [0.81 to 1.82] 0.353
Opioid dose 6 h (oxycodone mg equivalents) 5 (0,10) 5 (0,10) 0.61 [ 1.62 to 2.85] 0.592
Opioid dose to 24 h (oxycodone mg equivalents) 10 (0,30) 15 (5,30) 1.83 [ 1.35 to 5.01] 0.259
Opioid dose to 48 h (oxycodone mg equivalents) 30 (15,60) 35 (15,63) 3.20 [ 1.95 to 8.36] 0.223
Postoperative rescue anti-emetic use 382 (38.2%) 144 (41.03%) 1.21 [0.93 to 1.56] 0.154
1 210 (21.0%) 78 (22.3%)
2 128 (12.8%) 49 (14.0%)
>2 44 (4.4%) 17 (4.9%)
Pain score at 6 h
maximum 4 (0,6) 4 (0,6) 0.19 [ 0.21 to 0.59] 0.360
average 1.7 (0,3.5) 2 (0,4) 0.19 [ 0.09 to 0.48] 0.187
Breastfeeding prior to hospital discharge 897 (89.8%) 311 (88.9%) 0.95 [0.60 to 1.48] 0.697
Serum creatinine >0.9 mg/dL* 34 (28.3%) 10 (32.3%) NA 0.836
Change from pre-operative to postoperative creatinine (mg/dL)** 0.1 (0, 0.2) 0.1 (0, 0.3) NA 0.381
Data are number (%) or median (interquartile range). * Data available for 120 patients in the 15 mg group and 31 patients in the 30 mg group. ** Paired pre-operative and postoperative creatinine
values were available in 99 patients (77 in the 15 mg group and 22 in the 30 mg group). NA: not applicable due to small number of patients.

119
120 Intra-operative ketorolac 15 mg versus 30 mg for analgesia following cesarean delivery: a retrospective study
predictive of the dose selected. Therefore, we adjusted
for attending anesthesiologist and case urgency (P
<0.1) in the regression models.
There was no significant difference between the 15 mg
and 30 mg groups for opioid use in the first 6 h after
cesarean delivery (50.3% vs 52.0%; OR, 95% CI 1.13,
0.87 to 1.47). There were also no significant differences
between the two groups for any of the secondary out-
comes (Table 2).
Discussion
In this retrospective study, we found no difference in
opioid use after intra-operative ketorolac 15 mg vs
30 mg for post-cesarean analgesia.
There are limited data on optimal dosing of ketoro-
lac. De Oliveira et al. reported that ketorolac 60 mg
decreased postoperative pain and opioid consumption,
but that a 30 mg dose was not different from placebo
in general surgical patients.3 Motov et al. compared
three doses of ketorolac (10 mg, 15 mg and 30 mg) for
acute pain in the emergency department and reported
pain reduction at 30 min with all doses but without sig-
nificant differences between the groups.4 Duttchen et al.
found no difference in postoperative pain scores or opi-
oid consumption after intra-operative ketorolac 15 mg
or 30 mg in spine surgery.5
There are a few potential concerns with the use of
ketorolac, namely renal insufficiency and bleeding
risk.6,7 A previous systematic review in non-pregnant
patients suggested that the risk of renal injury was min-
imal in adults with normal kidney function.8 In our
cohort, we found no statistically significant difference
between the two ketorolac groups in the incidence of
renal dysfunction. However, this result must be inter-
preted with caution because we do not routinely check
creatinine values postoperatively. The risk of bleeding
complications with ketorolac might be dose-dependent.
In non-pregnant patients, Strom et al. reported a thresh-
old daily dose of 120 mg, above which the risk of gastro-
intestinal or surgical site bleeding increased significantly
and exponentially.9 The European Drug Agency recom-
mends an initial dose of ketorolac of 10 mg, followed by
10–30 mg every 4–6 h, with a maximum daily dose of
90 mg.10 Duttchen et al. did not observe any differences
in bleeding complications between 15 mg and 30 mg
doses used in spine surgery patients.5
There are several limitations to our study. This was a
single-center retrospective study. The choice of ketoro-
lac dose was according to physician preference and not
randomized. Our analysis suggests that the individual
attending anesthesiologist was an important factor in
determining the dose used. The fact that most anesthesi-
ologists used both doses was likely due to those physi-
cians always supervising another provider, so these
providers could also have had an impact on dose selec-
tion. It is, however, possible that case complexity or
anticipated level of postoperative pain may have influ-
enced the choice. Our analysis did indeed show that
intra-operative variables such as higher estimated blood
loss and comorbidities such as pre-eclampsia resulted in
a decision not to administer ketorolac, but did not
impact dose selection. We used estimated rather than
quantitative blood loss, and we do not routinely check
postoperative hemoglobin, so the change from pre- to
postoperative hemoglobin was not available. We had
postoperative creatinine data for a small number of
patients, so are unable to draw conclusions about possi-
ble differences between the two doses on postoperative
serum creatinine. Finally, the urgency of cesarean deliv-
ery might not be balanced between the groups, although
this was adjusted for in the final analysis. Furthermore,
a previous study has found that analgesic requirements
and pain scores are not significantly different between
scheduled and non-scheduled cesarean deliveries.11
In conclusion, our retrospective analysis suggests that
there is no difference in postoperative opioid use after
15 mg or 30 mg intra-operative ketorolac is used as part
of a multimodal analgesic regimen in women undergo-
ing cesarean delivery under neuraxial anesthesia.
Funding sources
This research did not receive any specific grant from
funding agencies in the public, commercial, or not-for-
profit sectors.
Declarations of interest
None.
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