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Original article 43

Pre-emptive intravenous ketorolac analgesia does not alter

the risk of bleeding after tonsillectomy in children
Waleed M. Abdelmageeda,c, Hesham F. Solimana, Mohamed A. Fatthallahb
a
Department of Anesthesia, Faculty of
Medicine, Ain-Shams University, Cairo,
b
Department of ENT, Faculty of Medicine,
Alazhar University, Demiatte, Egypt, cKing
Abdulaziz Naval Base Hospital, Jubail,
Kingdom of Saudi Arabia
Correspondence to Hesham Fathy Soliman,
MD, Alnoor Specialist Hospital, PO Box 6251,
Makkah 21955, Kingdom of Saudi Arabia
Tel: +966 502376651; fax: +966 125666837;
e-mail: hesham_fathy@hotmail.com
Received 12 September 2014
Accepted 10 December 2014
Ain-Shams Journal of Anesthesiology
2015, 08:43–49
Background
NSAIDs inhibit platelet aggregation and prolong bleeding time, which may augment the
risk of postoperative bleeding. We investigated the effects of pre-emptive analgesia with
intravenous ketorolac on intraoperative and postoperative hemorrhage with pediatric
tonsillectomy.
Patients and Methods
A total of 147 children, aged 2–7 years, scheduled for tonsillectomy with or without
adenoidectomy were randomized to receive a slow intravenous infusion of either ketorolac
1 mg/kg (ketorolac group, n = 74) or paracetamol 15 mg/kg (paracetamol group, n = 73) after
induction of anesthesia. Noninvasive hemoglobin was assessed preoperatively and several
times after surgery. Bleeding times were measured before and after surgery. Intraoperative
blood loss was estimated. Intensity of postoperative pain was measured using an objective
pain score. The incidence and severity of post-tonsillectomy bleeding were recorded until the
seventh postoperative day.
Results
There was no statistically significant difference in the estimated intraoperative blood loss
between ketorolac and paracetamol groups (2.4 ± 1.1 vs. 2.1 ± 0.8 ml/kg, respectively;
P = 0.061). Bleeding time increased between preoperative and postoperative assessments in
both groups, with significant postoperative elevation in the ketorolac group (P = 0.001). Both
groups were comparable regarding the perioperative noninvasive hemoglobin measurements.
The overall incidence of post-tonsillectomy bleeding was 5.4%, with no statistically significant
difference between ketorolac and paracetamol groups [5 (6.75%) vs. 3 (4.1%) patients,
respectively; P = 0.705]. Postoperative objective pain score were significantly lower in the
ketorolac group on postanesthesia care unit admission and at 1, 2, and 6 postoperative hours
(P < 0.05).
Conclusion
Pre-emptive ketorolac infusion during pediatric tonsillectomy provides superior postoperative
analgesia with no effect on intraoperative or postoperative clinical bleeding.

Keywords:
children, post-tonsillectomy bleeding, pre-emptive ketorolac analgesia, tonsillectomy

Ain-Shams J Anesthesiol 08:43–49

© 2015 Department of Anesthesiology, Intensive Care and Pain Managment,
Faculty of Medicine, Ain-Shams University, Cairo, Egypt
1687-7934

effects of opioids [4]. The oral and rectal formulations

Introduction
Tonsillectomy is a common surgical procedure in
childhood and is associated with severe postoperative
pain [1]. Management of post-tonsillectomy pain in
pediatric patients remains a challenge, as adequate pain
control is crucial to minimize crying (which increases
the risk of postoperative bleeding), ensure adequate
hydration, and resume regular oral intake as soon as
possible after surgery [2]. Traditionally, pain relief has
been provided by opioid analgesics; however, the risk
for postoperative nausea and vomiting (PONV), deep
sedation, and respiratory depression limit their use,
especially when the care of the child is the parents’
responsibility after day-case surgery [3]. Paracetamol is
a nonopioid analgesic and antipyretic medication that
acts at both the central and peripheral components
of the pain pathway, and is devoid of the detrimental
1687-7934 © 2015 Department of Anesthesiology, Intensive Care and Pain Management,
Faculty of Medicine, Ain-Shams University, Cairo, Egypt
of this agent have long been used to provide
postoperative analgesia in children; however, irregular
bioavailability of the paracetamol suppository [5] and
the temporary prohibition of oral intake limit their use
in the treatment of immediate post-tonsillectomy pain.
An i.v. form of paracetamol with more predictable
pharmacodynamic properties compared with its other
formulations has become available [6]. The safety
and efficacy of i.v. paracetamol in children have been
investigated in several publications [7,8].
NSAIDs are effectively used for pain relief following
tonsillectomy in children, with a lower risk for
PONV  [9]. They act by reducing prostaglandin
synthesis through inhibition of cyclo-oxygenase
(COX) enzymes I and II, with subsequent inhibition
of platelet aggregation; thus, NSAIDs may be linked
DOI: 10.4103/1687-7934.153937
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44 Ain-Shams Journal of Anesthesiology
to increased incidence of post-tonsillectomy bleeding
(PTB) [10]. Ketorolac is an intravenous NSAID that
has been found to be as effective as morphine for
relief of moderate to severe postoperative pain [11].
However, its effect on platelet aggregation with the
anticipated increased risk for PTB is still a subject of
debate among surgeons and anesthesiologists who have
been unwilling to use NSAIDs for post-tonsillectomy
analgesia. Therefore, the purpose of this study was to
evaluate the effect of the pre-emptive i.v. ketorolac
analgesia versus i.v. paracetamol on intraoperative and
postoperative clinical bleeding in children undergoing
tonsillectomy.
Patients and Methods
This prospective, randomized, double-blind, controlled
study took place in King Abdulaziz Naval Base
Hospital, Jubail, Kingdom of Saudi Arabia, from
December 2011 to May 2013. The protocol was
approved by the Hospital Ethics Committee and
registered with the Australian New Zealand Clinical
Trials Registry (http://www.ANZCTR.org.au/
ACTRN12613001203741.aspx). Written informed
consent was obtained from the guardian of each child.
We studied 147 children of ASA physical status I, of
both sexes, aged 3–7 years, scheduled for tonsillectomy
with or without adenoidectomy. All patients enrolled
in this study had normal blood counts, with normal
coagulation profile [prothrombin time, activated
partial thromboplastin time, platelet count, and
bleeding time (BT)]. Exclusion criteria included the
use of paracetamol or NSAIDs within 6 h, or any other
analgesic medication within 12 h before surgery, and a
known allergy to any of the study drugs. Hemoglobin
(Hb) level was measured in the laboratory as part of
the routine preoperative preparation for tonsillectomy
at the hospital. In addition, noninvasive hemoglobin
level (SpHb) was assessed at the same time when blood
was drawn from the child for the routine preoperative
laboratory investigations, using multiwavelength pulse
oximetry (MASIMO Radical-7 Signal Extraction
Pulse Co-Oximeter; Masimo Corporation, Parker
Irvine, California, USA).
No premedication was given, and all children had been
fasting from solid food for 8 h before operation, with
clear liquids permitted until 3 h before surgery. At the
operating theatre, monitors to record intraoperative
vital measurements [ECG, noninvasive systolic
and diastolic blood pressure, and peripheral oxygen
saturation (SpO2)] were attached. All children
received standardized general anesthesia, started by
inhalational induction with sevoflurane, and 60%
nitrous oxide in oxygen, followed by placement of an
i.v. cannula. Tracheal intubation was facilitated with
0.5 mg/kg atracurium. An oxygen and nitrous oxide
mixture (40  :  60% respectively) with sevoflurane
1.5–2.5 volume% in 3 l/min fresh gas flow was used for
maintenance of anesthesia, and mechanical ventilation
was started with pressure-controlled ventilation at
15–20 cm H2O to keep the end-tidal carbon dioxide at
30–35 mmHg. Sevoflurane concentration was adjusted
to maintain the child’s heart rate and blood pressure
within 30% of the preoperative values.
After induction of anesthesia and before surgical
incision, the children were randomized, by using a
computer generated random list, into one of two
groups — the ketorolac group (group K) and the
paracetamol group (group P) – to receive a slow i.v.
infusion over 15 min of either ketorolac 1 mg/kg
(ketorolac tromethamine; Hospira Inc., Lake Forest,
Illinois, USA) (group K) or paracetamol 15 mg/kg
(Perfalgan; UPSA, Bristol Myers Squibb, 304, avenue
du Docteur Jean Bru 47000 AGEN, France) (group
P). Both medications were diluted with 0.9% saline
to a total volume of 40 ml. This volume was deducted
from the total i.v. fluid administered (dextrose 5% in
0.45% saline, at a rate of 7 ml/kg/h). The anesthesia
technician, who was not involved in the data collection,
prepared identical infusions under aseptic conditions.
All operations were performed by one of three surgeons
(two consultants and one senior registrar) following
a standardized surgical technique, with bilateral
dissection of the tonsils and bipolar diathermy for
hemostasis. Intraoperative blood loss was estimated by
recording the volume of blood in the calibrated suction
canister and counting the blood-soaked gauzes that
had been used for packing the bleeding sites after tonsil
removal (one soaked gauze equalled 5 ml of blood).
On completion of surgery, sevoflurane administration
was stopped, and atropine 20 μg/kg with neostigmine
50 μg/kg was used to antagonize the residual
neuromuscular block. The trachea was extubated after
recovery of adequate spontaneous ventilation.
Following surgery, the patients were kept on oxygen
supplementation through a face mask at 6 l/min and
were transferred to the postanesthesia care unit (PACU)
for continuous monitoring. SpHb measurement was
assessed on arrival at the PACU and repeated at 12 and
24 h postoperatively, and another measurement was
obtained on the seventh postoperative day (POD7).
On admission to the PACU, BT test using Ivy’s method
was also performed by a laboratory technician who was
blinded to the treatment group.
In the PACU and the surgical ward, pain intensity was
assessed by an anesthesiologist blinded to the treatment
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Pre-emptive intravenous ketorolac Abdelmageed et al. 45

group using an objective pain score (OPS) immediately Hb level. It was estimated that a sample of 70 patients
upon PACU admission, followed by 30 min, 1, 2, 4, and per group would have a power of 82% to detect a
6 h postoperatively. The OPS used was a modification medium effect size (d) of 0.5 as regards the outcome
of the pain score described by Hannallah et al. [12] and measures using a two-sided U-test and setting the type
took into account the child’s blood pressure, crying, I error at 0.05.
movement, and agitation, with each variable scoring
0–2 points (0 being the best and 2 being the worst). Data were analyzed on a personal computer using the
This scale had been previously used for pain scoring IBM© SPSS© Statistics, version 21 (IBM© Corp.,
after pediatric tonsillectomy [6]. Rescue analgesic Armonk, New York, USA). The Shapiro – Wilk test
medication consisting of i.v. meperidine 0.25 mg/kg, was used to test the normality of numerical data
to a total dose of 1 mg/kg, was administered if OPS distribution.
was greater than 4 and the pain score was reassessed
every 10 min until a score less than 4 was achieved. The Normally distributed data were presented as mean
time to administer the first rescue analgesics (defined (SD) and the unpaired t-test was used for intergroup
as the period between tracheal extubation to the first comparisons. Skewed data were presented as median
administration of meperidine) and the total amount of (interquartile range) and the Mann–Whitney U-test
meperidine given were recorded. If still in pain despite was used to compare between-group differences. For
receiving the maximum dose of meperidine, the child comparison of paired skewed data, the Wilcoxon
was given a paracetamol suppository of 35 mg/kg and signed rank test was used. Repeated-measures analysis
excluded from the study. At 3 h after surgery, the parent of variance was used to compare differences among
or a nurse started to offer the child oral liquids, and serial measures.
once he/she was able to tolerate oral fluids pain was
Categorical data were presented as ratio or number
treated every 6 h with oral paracetamol at 20 mg/kg
(percentage) and differences between the two groups
every 6 h. The time to first oral intake was also recorded.
were compared using the χ2-test or Fisher’s exact test,
The incidence of postoperative vomiting was documented when appropriate.
throughout the first 24 h after surgery. If a child had
P values less than 0.05 were considered statistically
two or more episodes of vomiting, ondansetron 50 μg/
significant.
kg i.v. (maximum 4 mg) was used as a rescue antiemetic.
The incidence of PTB was recorded over a 7-day period.
Bleeding severity was assessed and classified as mild
(mild oozing of blood or spitting of blood-tinged saliva Results
reported by the parents), moderate (active bleeding that A total of 147 children completed the study. The
required hospital admission for conservative treatment), flowchart of patients throughout the study is presented
or severe (persistent bleeding; the child has to be taken to in Fig. 1. The groups were comparable for patient
the operative room for bipolar diathermy and/or suture characteristics and duration of surgery and anesthesia.
ligature under general anesthesia). The children were There was no statistically significant difference in the
discharged from hospital on the second postoperative estimated intraoperative blood loss between the two
day and were followed up for 7 days postoperatively. groups (P = 0.061) (Table 1). The mean heart rate,
The parents were instructed to contact the Emergency blood pressure, and SpO2 values throughout the study
Department in case of postoperative bleeding, and PTB period were statistically similar in the two groups.
was defined to them as spitting or oozing of blood Perioperative BTs are shown in Table 2. The values
from the mouth. At POD7, the patients arrived at increased between preoperative and postoperative
the outpatient department, where they were examined
and the last SpHb measurement was taken. Any other
Table 1 Patient characteristics and operative data
postoperative adverse effects were recorded.
Variables Ketorolac Paracetamol P
group group value
(n = 74) (n = 73)
Statistical methods
Age (years) 4.1 (1.3) 3.9 (0.9) 0.281
The required sample size was calculated using Sex (M/F) 49/25 41/32 0.280
G*Power© software, version 3.1.0 (Institut für Weight (kg) 18.2 (5.1) 16.9 (3.9) 0.085
Experimentelle Psychologie, Heinrich Heine Tonsillectomy/adenotonsillectomy 28/46 34/39 0.365
Universität, Düsseldorf, Germany). Duration of surgery (min) 37 (13.6) 40 (9.2) 0.126
Duration of anesthesia (min) 48 (16.1) 52 (11.6) 0.086
The primary outcome measures were the difference Intraoperative blood loss (ml/kg) 2.4 (1.1) 2.1 (0.8) 0.061
between the two groups as regards the pain scores and Data are presented as mean [SD] or ratio.
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46 Ain-Shams Journal of Anesthesiology

assessments in both groups, with statistically significant Table 2 Perioperative bleeding times
elevation in the ketorolac group (P = 0.001). However, Variables Ketorolac Paracetamol P valuea
group (n = 74) group (n = 73)
all postoperative BT values were still within the normal
range in the two groups. Preoperative BT (min) 3.6 (3.3–4.1) 3.5 (3.4–3.9) 0.600
Postoperative BT (min) 4.5 (4.3–5.1) 3.7 (3.5–4.3) <0.0001

Analysis of the postoperative pain scores revealed P valueb <0.0001 <0.0001

Data are presented as median [interquartile range]; BT, bleeding
significantly lower OPS in the ketorolac group
time; aFor intergroup difference [Mann–Whitney U-test];
on admission to the PACU and at 1, 2, and 6 h b
For within-group difference [Wilcoxon signed ranks test].
after surgery (P  <  0.05) (Table 3). The cumulative
postoperative meperidine consumption was Table 3 Postoperative pain scores
statistically higher in the paracetamol group than Variables Ketorolac Paracetamol P value
in the ketorolac group (7.5 ± 3.1 vs. 6.4 ± 2.9 mg, group (n = 74) group (n = 73)
respectively; P = 0.012), with significantly shorter Pain score
time to first analgesic administration compared with On admission to PACU 6 (5–6) 6 (5–7) 0.009
group K (28 ± 12.1 vs. 32.4 ± 8.7 min, respectively; 30 min after surgery 4 (4–6) 5 (4–6) 0.052
P  =  0.012). The ketorolac-treated patients tolerated 1 h after surgery 4 (3–5) 3 (2–4) 0.001
oral fluids faster than did those receiving paracetamol 2 h after surgery 3 (2–4) 4 (2.75–5) 0.001
3 h after surgery 2 (1–3) 2 (2–3) 0.772
with a significantly lower mean time to first oral intake
4 h after surgery 2 (2–3) 2 (2–3) 0.795
(4.9 ± 1.5 vs. 5.6 ± 2.0 h, respectively; P = 0.018).
6 h after surgery 2 (1–2) 2 (2–2) 0.011
Data are presented as median [interquartile range];
There was no significant difference between PACU, postanesthesia care unit.
preoperative laboratory Hb level and SpHb obtained
at the same preoperative time (P  >  0.05) in the
Table 4 Perioperative hemoglobin levels
two groups. There were no statistically significant
Variables Ketorolac Paracetamol P
differences in the perioperative SpHb assessments group (n = 74) group (n = 73) value
between the two groups until POD7 (Tables 4–6 and Preoperative laboratory 11.9 (1.2) 12.2 (1.6) 0.200
Fig. 2). The overall incidence of PTB in this study hemoglobin (g/dl)
was 5.4%. In the ketorolac group, 5 (6.8%) patients Preoperative SpHb (g/dl) 12.0 (1.1) 12.3 (1.6) 0.187
suffered from PTB compared with 3 (4.1%) patients SpHb on admission to 12.0 (1.1) 12.2 (1.4) 0.337
PACU (g/dl)
in paracetamol group, with no statistically significant
SpHb 24 h after 11.7 (1.0) 11.9 (1.2) 0.274
difference between the two groups (P = 0.705). In the surgery (g/dl)
ketorolac group, one child had persistent bleeding on SpHb on 7th 11.6 (1.4) 11.8 (1.6) 0.421
postoperative day (g/dl)
Figure 1 Data are presented as mean [SD]; PACU, postanesthesia care
unit; SpHb, noninvasive hemoglobin level.

Figure 2

Change in perioperative noninvasive hemoglobin in the two study

groups. T1, baseline; T2, at PACU; T3, at 24 h after surgery; T4,
at 7 days after surgery. Bars represent mean. Error bars represent
95% CI. CI, confidence interval; PACU, postanesthesia care unit;
Flowchart of children throughout the study. SpHb, noninvasive hemoglobin.
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Pre-emptive intravenous ketorolac Abdelmageed et al. 47

Table 5 Repeated-measures analysis of variance for change in perioperative noninvasive hemoglobin level
Test Source of variation Sum of squares d.f.a Mean square F P value
Test of between-subjects effects Group 0.573 1 0.573 0.46 0.501
Residual 182.305 145 1.257
Test of within-subjects effects Factor 6.858 2.778 2.469 2.02 0.115
Group × factor interaction 2.992 2.778 1.077 0.88 0.444
Residual 491.572 402.749 1.221
F, F-statistic; aCorrected to sphericity by the Huynh-Feldt method [Epsilon [ε] = 0.901 by the Greenhouse – Geisser method and ε = 0.926
by the Huynh-Feldt method].

Table 6 Pairwise comparisons of noninvasive hemoglobin level in the two study groups
SpHbi SpHbJ Group K (n = 74) Group P (n = 73)
d SE P value a
95% CI d SE P valuea 95% CI
Baseline At PACU −0.13 0.17 1.0 −0.60 to 0.34 −0.03 0.18 1.0 −0.51 to 0.46
At 24 h 0.01 0.17 1.0 −0.46 to 0.48 0.40 0.18 0.202 −0.10 to 0.90
At 7 days 0.03 0.2 1.0 −0.51 to 0.57 0.21 0.21 1.0 −0.36 to 0.77
At PACU At 24 h 0.14 0.05 0.069 −0.01 to 0.29 0.43 0.18 0.118 −0.06 to 0.91
At 7 days 0.17 0.18 1.0 −0.32 to 0.65 0.23 0.18 1.0 −0.25 to 0.71
At 24 h At 7 days 0.03 0.18 1.0 −0.47 to 0.52 −0.19 0.17 1.0 −0.66 to 0.27
95% CI, 95% confidence interval of difference; d, mean difference; PACU, postanesthesia care unit; SpHb, noninvasive hemoglobin;
a
Bonferroni-corrected.

the day of surgery and returned to the operative room
for hemostasis under general anesthesia; the other four
patients developed mild secondary hemorrhage on
POD5 to POD7, which required no treatment. Three
patients receiving paracetamol developed PTB; one
had primary hemorrhage that necessitated surgical
intervention, and two others experienced moderate
bleeding that occurred between POD4 and POD7 and
needed conservative management. All eight patients
bled only once and none of them needed allogeneic
blood transfusion.
The overall incidence of postoperative emesis was
24.5%. Postoperative vomiting occurred in 16 (21.6%)
patients in the ketorolac group versus 20 (27.4%)
patients in the paracetamol group, with no statistically
significant difference between the two groups
(P = 0.448), in addition to a statistically similar number
of patients who were given ondansetron for multiple
emesis episodes [9 (12.2%) vs. 14 (19.2%) patients,
respectively; P = 0.265].
Discussion
In this study, the effect of pre-emptive intraoperative
ketorolac infusion of 1 mg/kg on intraoperative and
postoperative bleeding in pediatric tonsillectomy
was evaluated and compared with 15 mg/kg i.v.
paracetamol infusion, and no significant statistical
difference was recorded between the groups regarding
the estimated intraoperative blood loss, perioperative
SpHb values, or frequency and severity of PTB.
Moreover, our results revealed that patients treated
with ketorolac had enhanced postoperative analgesia
with lower consumption of rescue analgesics and faster
resumption of oral intake.
Despite the fact that all NSAIDs have antiplatelet effect
and prolong the BT, published data regarding their
effect on intraoperative and postoperative bleeding
during tonsillectomy have been conflicting [13–16]. It
should be noted that most anesthesiologists are aware
that the skill and experience of the surgeon, together
with the operative technique used, are important
factors to be considered whenever PTB is a concern.
In addition, the reversible effect of ketorolac on platelet
function is short-lived, and limited to the time the
drug is present in high blood concentration. Because
of the short half-life of ketorolac (∼5–6 h), platelet
function is expected to return to normal within 24 h
of a single dose administration of the drug (after 5
to 6 drug half-lives) [17], and any bleeding episode
that could be related to a single intraoperative dose
of ketorolac would have to occur in the immediate
postoperative period, or within the first 24 h. Therefore,
the episodes of secondary hemorrhage that occurred in
the patients treated with ketorolac in the current study
between POD5 and POD7 might not be due to a
single intraoperative dose of ketorolac as they occurred
at a time well after the drug had been eliminated from
the body. Those bleeding events might be caused by
dehiscence of the eschar occurring several days after
surgery.
BT is one of the first-line screening tests of platelet
function with a wide normal range of 2–7 min [18].
This test is subjected to a lot of confounding factors,
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48 Ain-Shams Journal of Anesthesiology
including the type of technique and the skill and
experience of the technician performing it. A normal
BT does not imply normal hemostasis and the result
of the test has been shown not to correlate with
bleeding at other sites [18]. In the current study, the
postoperative BT tests were significantly prolonged
in the patients treated with ketorolac versus those
receiving paracetamol, although all postoperative
BT values in the groups were still within the normal
range. Nevertheless, prolongation of BT in the patients
receiving ketorolac in this study, which probably
indicates affection of platelet aggregation, was not
reflected on the intraoperative clinical bleeding and
was not associated with hemodynamic compromise or
increased risk for postoperative bleeding events. The
agreement of SpHb measurements with laboratory Hb
levels was verified to ensure the accuracy and precision
of the pulse co-oximeter in offering an accurate, real-
time, and noninvasive assessment of Hb. The ease
in obtaining perioperative Hb values noninvasively
enabled us to perform frequent postoperative
assessments in this study to determine any decrease
in Hb level that could be related to intraoperative or
postoperative hemorrhage, to detect clinical bleeding
based on objective laboratory values.
The use of i.v. paracetamol for postoperative pain
control is gradually increasing, and several studies in
the literature have demonstrated the analgesic and
opioid-sparing effect of this agent [19]. However,
when paracetamol is used alone for post-tonsillectomy
pain, it often provides insufficient analgesia [2]. In the
present study, analysis of OPS revealed significantly
higher values in children receiving paracetamol
following surgery, with shorter time to first analgesic
administration and significant increase in the
postoperative meperidine consumption compared
with the other group of patients. We therefore share
the view of other authors [20,21] that paracetamol,
although safe, is not effective as a sole analgesic in
pediatric tonsillectomy.
Further, the use of ketorolac in this study was associated
with shorter time to first oral intake. A delay in starting
and tolerating postoperative oral fluids, as well as
inadequate oral feeding because of pain and vomiting,
can prolong the hospital stay and increase the risk
of dehydration in the postoperative period. NSAIDs
decrease the levels of inflammatory mediators generated
locally at the site of tissue disruption through direct
inhibition of the COX enzyme activity, thus blocking
the conversion of arachidonic acid to prostaglandins
and leukotriene. These mediators, in addition to
initiating the inflammatory cascade, sensitize the
pain nerve endings to various noxious stimuli [22].
Therefore, by decreasing the inflammatory response and
providing adequate postoperative analgesia, ketorolac
can play a role in the process of re-establishment of the
normal physiological mechanisms of swallowing. In
contrast, paracetamol has been shown to have a weak
anti-inflammatory action [23].
PONV are common side effects after tonsillectomy. As
our results showed, the overall incidence of postoperative
vomiting in this study was lower than that reported in
several previous studies [24,25]. This could be partly
attributed to the absence of opioids in our anesthetic
regimen; besides, a possible central antiemetic effect of
both drugs used in this study could not be ruled out.
There is a lot of evidence that NSAIDs have a central
mechanism of action that augments the peripheral
mechanism. This effect may be the result of interference
with the formation of prostaglandins or by blocking
the release of serotonin (5-hydroxytryptamine; 5-HT)
within the central nervous system [26]. A similar
central effect of paracetamol had been described [4].
We believe that, despite the availability of various
therapeutic approaches to treat post-tonsillectomy pain in
children, NSAIDs remain an attractive choice, although
the perioperative use of COX-2-selective NSAIDs
had been shown to provide similar analgesic effects to
conventional NSAIDs when used for acute pain, with
minimal side effects. However, the use of NSAIDs
selective for COX-2 for pain management in the pediatric
population is rare, and the previously raised controversies
regarding the involvement of these drugs in ischemic
heart disease in adults have limited their use [27].
Conclusion
In conclusion, we found that the pre-emptive use
of a single dose of i.v. ketorolac during pediatric
tonsillectomy provided superior postoperative analgesia
and was not associated with increased incidence of
intraoperative or postoperative bleeding.
Acknowledgements
Conflicts of interest
There are no conflicts of interest.
References
1 Walner DL, Karas A. Standardization of reporting post-tonsillectomy
bleeding. Ann Otol Rhinol Laryngol 2013; 122:277–282.
2 Safavi M, Honarmand A, Habibabady MR, Baraty S, Aghadavoudi O.
Assessing intravenous ketamine and intravenous dexamethasone
separately and in combination for early oral intake, vomiting and
postoperative pain relief in children following tonsillectomy. Med Arh 2012;
66:111–115.
3 Kocum AI, Sener M, Caliskan E, Bozdogan N, Micozkadioglu D,
Yilmaz I, Aribogan A. Intravenous paracetamol and dipyrone for
postoperative analgesia after day-case tonsillectomy in children: a
[Downloaded free from http://www.asja.eg.net on Friday, April 16, 2021, IP: 188.139.228.210]
prospective, randomized, double blind, placebo controlled study. Braz
J Otorhinolaryngol 2013; 79:89–94.
4 Duggan ST, Scott LJ. Intravenous paracetamol (acetaminophen). Drugs
2009; 69:101–113.
5 Kraemer FW, Rose JB. Pharmacologic management of acute pediatric
pain. Anesthesiol Clin 2009; 27:241–268.
6 Uysal HY, Takmaz SA, Yaman F, et al. The efficacy of intravenous
paracetamol versus tramadol for postoperative analgesia after
adenotonsillectomy in children. J Clin Anesth 2011; 23:53–57.
7 Jahr JS, Lee VK. Intravenous acetaminophen. Anesthesiol Clin 2010;
28:619–645.
8 Murat I, Baujard C, Foussat C, Guyot E, Petel H, Rod B, Ricard C.
Tolerance and analgesic efficacy of a new i.v. paracetamol solution in
children after inguinal hernia repair. Paediatr Anaesth 2005; 15:663–670.
9 Lewis SR, Nicholson A, Cardwell ME, Siviter G, Smith AF. Nonsteroidal
anti-inflammatory drugs and perioperative bleeding in paediatric
tonsillectomy. Cochrane Database Syst Rev 2013; 7:CD003591.
10 Yaman H, Belada A, Yilmaz S. The effect of ibuprofen on postoperative
hemorrhage following tonsillectomy in children. Eur Arch Otorhinolaryngol
2011; 268:615–617.
11 Rusy LM, Houck CS, Sullivan LJ, Ohlms LA, Jones DT, McGill TJ,
Berde CB. A double-blind evaluation of ketorolac tromethamine versus
acetaminophen in pediatric tonsillectomy: analgesia and bleeding. Anesth
Analg 1995; 80:226–229.
12 Hannallah RS, Broadman LM, Belman AB, Abramowitz MD, Epstein BS.
Comparison of caudal and ilioinguinal/iliohypogastric nerve blocks
for control of post-orchiopexy pain in pediatric ambulatory surgery.
Anesthesiology 1987; 66:832–834.
13 Judkins JH, Dray TG, Hubbell RN. Intraoperative ketorolac and
posttonsillectomy bleeding. Arch Otolaryngol Head Neck Surg 1996;
122:937–940.
14 Moiniche S, Romsing J, Dahl JB, Tramer MR. Nonsteroidal antiinflammatory
drugs and the risk of operative site bleeding after tonsillectomy: a
quantitative systematic review. Anesth Analg 2003; 96:68–77.
15 Marret E, Flahault A, Samana CM, et al. Effect of postoperative,
nonsteroidal, anti-inflammatory drugs on bleeding risk after tonsillectomy.
Pre-emptive intravenous ketorolac Abdelmageed et al. 49
Meta-analysis of randomised, controlled trials. Anaesthesiology 2003;
98:1497–1502.
16 Riggin L, Ramakrishna J, Sommer DD, Koren G. A 2013 updated
systematic review & meta-analysis of 36 randomized controlled trials; no
apparent effects of non steroidal anti-inflammatory agents on the risk of
bleeding after tonsillectomy. Clin Otolaryngol 2013; 38:115–129.
17 Niemi TT, Backman JT, Syrjala MT, Viinikka LU, Rosenberg PH.
Platelet dysfunction after intravenous ketorolac or propacetamol. Acta
Anaesthesiol Scand 2000; 44:69–74.
18 Bain BJ, Foster T, Baner T. An assessment of the sensitivity of three
bleeding time techniques. Scand J Haematol 1983; 30:311–316.
19 Khan ZU, Iqbal J, Saleh H, et al. Intravenous paracetamol is as effective
as morphine in knee arthroscopic day surgery procedures. Pak J Med Sci
2007; 23:851–853.
20 Rømsing J, Ostergaard D, Drozdziewicz D, et al. Diclofenac or
acetaminophen for analgesia in paediatric tonsillectomy outpatients. Acta
Anaesthesiol Scand 2000; 44:291–295.
21 Mather SJ, Peutrell JM. Postoperative morphine requirements, nausea
and vomiting following anaesthesia for tonsillectomy. Comparison of
intravenous morphine and non-opioid analgesic techniques. Paediatr
Anaesth 1995; 5:185–188.
22 McCormack K, Brune K. Dissociation between the antinociceptive and
anti-inflammatory effects of the nonsteroidal anti-inflammatory drugs. A
survey of their analgesic efficacy. Drugs 1991; 41:533–547.
23 Lee SY, Lee WH, Lee EH, Han KC, Ko YK. The effects of paracetamol,
ketorolac, and paracetamol plus morphine on pain control after
thyroidectomy. Korean J Pain 2010; 23:124–130.
24 Kokki H, Salonen A. Comparison of pre- and postoperative administration
of ketoprofen for analgesia after tonsillectomy in children. Paediatr
Anaesth 2002; 12:162–167.
25 Ang C, Habre W, Sims C. Tropisetron reduces vomiting after tonsillectomy
in children. Br J Anaesth 1998; 80:761–763.
26 Cashman JN. The mechanisms of action of NSAIDs in analgesia. Drugs
1996; 52:13–23.
27 Moodley I. Review of the cardiovascular safety of COXIBs compared to
NSAIDS. Cardiovasc J Afr 2008; 19:102–107.