Recurrent Acute Tonsillitis Clinical Trial
Official title:
KITS Study -Ketorolac In Tonsillectomy Surgery: a Double Blinded, Randomized Clinical Trial
Our group wishes to test the novel hypothesis that intraoperative use of ketorolac in pediatric patients undergoing tonsillectomy reduces post-operative nausea and vomiting, postoperative pain scores, subsequent narcotic use, and length of hospital stay without adversely affecting post-operative bleed risk, when compared to placebo, in a double-blind, randomized controlled trial.
Intraoperative analgesia has a tremendous theoretical potential to decrease postoperative
pain, and thus narcotic requirement and length of subsequent hospital stay. There is indeed a
dearth of evidence with respect to the clinical effectiveness of such analgesia.
Tonsillectomy lends itself particularly well to the use of intraoperative analgesia;
post-operative pain scores are high, and the majority of recipients are pediatric patients—a
population in which minimization of post-operative narcotic use is a priority.
The effectiveness of intraoperative analgesia for the preemptive management of postoperative
pain, nausea and vomiting in tonsillectomy remains controversial. Pre-emptive analgesia was
first conceptualized in 1983, with Woolf's work on a postulated central component of
postinjury pain hypersensitivity. Tissue injury is typified by post-stimulus sensory
disturbances that give rise to continuing pain, a hypersensitivity to further noxious
stimuli, as well as pain in response to otherwise innocuous stimuli. These features are
attributable to both a reduction in the threshold of skin nociceptors, as well as an increase
in the excitability of the central nervous system (CNS) to noxious stimuli. Much experimental
data has shown pre-injury analgesia as being superior to post-injury analgesia in terms of
minimizing subsequent CNS excitability.
Clinically, the effectiveness of such analgesia has shown to be highly variable with respect
to anatomical area, surgical type, as well as analgesic used and its route of administration.
A Meta-analysis by Cliff et al. reviewed 66 studies with respect to the primary outcomes of
pain intensity scores, supplemental analgesic consumption, and time to first analgesic
consumption, and demonstrated that preemptive administration of NSAIDs was superior to that
of epidural analgesia, local anesthetic wound infiltration, systemic NMDA receptor
antagonists, and systemic opiods.
Ketorolac tromethamine (Toradol) is a parenteral, nonsteroidal anti-inflammatory drug that
has been used extensively to provide postoperative analgesia. In a prospective, randomized
double-blind study of 57 children undergoing outpatient adenotonsillectomy, Keidan et al.
found ketorolac to be comparable to fentanyl in terms of both post-operative nausea and
vomiting and pain scores. One study showed that intraoperative ketorolac (60 mg IV) with
fentanyl (2 micrograms/kg IV), compared to fentanyl and placebo, administered at the
induction of anesthesia resulted in significant opioid sparing, decreased pain scores, lower
incidence of nausea and vomiting and earlier discharge compared to fentanyl and placebo in
patients undergoing diagnostic laparoscopy.
There is a theoretical risk of post-operative bleeding with use of Toradol, on account of its
inhibition of platelet aggregation and prolonging of bleeding time. However, in a
meta-analysis of 13 trials comprising 955 children undergoing tonsillectomy, Cardwell et al.
found that postoperative NSAIDs did not significantly alter number of perioperative bleeding
events requiring surgical intervention. At present, it is common practice by some clinicians
at the Stollery Children's hospital for pediatric patients who are undergoing standard
electrocautery adenotonsillectomy to receive intraoperative ketorolac. Its role in improving
post-operative pain and possible risk of increasing post-operative bleeding remains
controversial.
i Woolf CJ: Evidence for a central component of post-injury pain hypersensitivity. Nature
1983; 308: 386-8
ii Coderre TJ, Catz J, Vaccarino AL, Melzack R: Contribution of central neutoplasticity to
pathological pain: Review of clinical and experimental evidence. Pain 1993; 52: 259-85
iii Aida S, Baba H, Yamakura T, MD, Taga K, Fukuda S, Shimoji K: The Effectiveness of
Preemptive Analgesia Varies According to the Type of Surgery: A Randomized, Double-Blind
Study. Anesth Analg 1999;89: 711 ivOng CKS, Lirk P, Seymour RA, Jenkins BJ: The Efficacy of
Preemptive Analgesia for Acute Postoperative Pain Management: A Meta-Analysis. Anesth Analg
2005;100:757-773
v Keidan I, Zaslansky R, Eviatar E, Segal S, Sarfaty SM. Intraoperative ketorolac is an
effective substitute for fentanyl in children undergoing outpatient adenotonsillectomy.
Paediatric Anaesthesia. 14(4):318-23, 2004 Apr.
vi Green CR, Pandit SK, Levy L, Kothary SP, Tait AR, Schork MA Intraoperative ketorolac has
an opioid-sparing effect in women after diagnostic laparoscopy but not after laparoscopic
tubal ligation. Anesthesia & Analgesia. 82(4):732-7, 1996 Apr.
vii Cardwell M, Siviter G, Smith A Non-steroidal anti-inflammatory drugs and perioperative
bleeding in paediatric tonsillectomy. Cochrane Database of Systematic Reviews. Issue: 2
Article: CD003591, 2005
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