Adenotonsillectomy is one of the most frequent surgeries performed in pediatric
population in the United States mainly due to conditions such as sleep disordered
breathing and recurrent tonsillitis. However, postoperative pain control following
adenotonsillectomy still offers great challenges to anesthesiologists. Postoperative pain
has been the most common adverse effect in post-anesthesia care unit (PACU) for children
undergoing tonsillectomies and postoperative pain is also correlated with emergence
agitation, ileus, delayed mobilization, prolonged hospital stays, the development of
chronic pain syndromes, and postoperative nausea and vomiting (PONV). Therefore, benefits
of effective pain control are many fold: improving patient/family satisfaction, reducing
the risk of postoperative bleeding due to emergence agitation, decreasing the incidence
of PONV, and cutting down clinical symptoms related to opioid overdose.
To better control postoperative pain, pre-operative and intraoperative pain management
have been the key. Preventative analgesic interventions may provide protection against
the development of persistent postoperative pain. Although opioid derivatives such as
fentanyl and morphine are mainstays for the perioperative management of
post-tonsillectomy pain, opioid consumption is positively correlated with clinical
adverse events such as PONV, opioid overdose, and over-sedation. Especially for pediatric
patients with severe obstructive sleep apnea (OSA), opioids may depress ventilation and
lead to further airway obstruction, resulting in desaturation of blood oxygen, and even
death. Multi-modal pain control includes use of combinations of opioids with selective
alpha2-adrenergic agonist such as dexmedetomidine and nonsteroidal anti-inflammatory
drugs (NSAIDS) such as ketorolac, are frequently used for analgesia in children
undergoing tonsillectomies. Dexmedetomidine is a selective alpha-2 adrenergic receptor
agonist that directly acts on the peripheral nervous system, causing a dose-dependent
inhibition of C-fibers and Aα-fibers. Non-selective NSAIDS have been shown to function
both peripherally and centrally in nociception. NSAIDs act at the peripheral nociceptors
by blocking the cyclooxygenase (COX) enzyme that inhibits the conversion of arachidonic
acid to prostaglandins, thereby preventing the sensitization of pain receptors in
response to injury. Centrally, NSAIDs inhibit prostaglandin E2 (PGE2) production in the
spinal dorsal horn via COX-2, activate medullary and cortical brain regions involved in
the descending inhibitory pain cascade, result in central sensitization and a lower pain
threshold in the surrounding uninjured tissue.
Among NSAIDS, Ketorolac tromethamine (Toradol) is the first approved for parenteral use
in 1990 in the United States. Despite its variety of clinical indications, it is mainly
administered for the management of postoperative pain. It has strong analgesic
properties, with a dose of 30 mg intramuscular (IM) offering similar analgesia as 12 mg
of morphine. The strong analgesic properties of reducing opioid requirements make it a
good candidate in multi-modal pain management of post-tonsillectomy pain. Unlike opioid
analgesics, ketorolac does not depress ventilation, and is not associated with nausea and
vomiting, urinary retention or sedation. When combined with an opioid, ketorolac exhibits
significant opioid-sparing effects, allowing a lower dosage of opioid to be used.
Clinical studies in children and adults show that the synergistic action of ketorolac and
opioids improves the degree and quality of pain relief, and reduces the incidence of
opioid-related adverse effects such as respiratory depression, PONV, and ileus. However,
similar to other non-selective Cox enzyme inhibitors, ketorolac has several adverse
effects including gastrointestinal (GI) bleeding, renal impairment, liver dysfunction,
possible allergic reactions, and disruption of platelet aggregation through the
inhibition of thromboxane A. However, the evidence of increased bleeding is conflicting.
A meta-analysis suggested that there was no consensus on the increased risk of bleeding
when NSAIDS such as ketorolac are given to pediatric patients undergoing tonsillectomy.
There are other analyses to support that conclusion.
Despite of these findings, perioperative ketorolac usage, especially in pediatric
tonsillectomy surgery, is very limited.