Evaluation of Perioperative Usage of Ketorolac on Postoperative Pain Reduction in Pediatric Patients with Adenotonsillectom

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. Philips-Reed et al conducted a metanalysis 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 their conclusion.

Despite of these findings, perioperative ketorolac usage, especially in pediatric tonsillectomy surgery, is very limited.