Page 25 - CASA Bulletin of Anesthesiologisy 2022 9(6)-1 (3)

Vol. 9, No 6, 2022

Somatic pain is due to production of inflammatory pain mediators resulting from tissue
damage. NSAIDs (ie. ketorolac) and selective cyclooxygenase-2 inhibitors (ie. celecoxib) have
been used to manage somatic surgical pain by inhibiting the production of these inflammatory
mediators. Preoperative celecoxib use has shown to reduce postoperative morphine consumption,
pain, nausea and vomiting . Preemptive analgesia with COX-2 inhibitors has shown to improve
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postoperative pain scores and decrease opioid consumption while increasing patient satisfaction
. Due to the lack of COX-2 enzyme in platelets, COX-2 inhibitors do not affect platelet function
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or increase perioperative bleeding.

The role of COX-2 in bone resorption and healing has been demonstrated through many
studies. Following bone injury, prostaglandin synthesis and COX-2 expressions are elevated
during the first two weeks to promote bone healing. For this reason, there has been concerns that
COX-2 inhibitors may interfere with proper bone formation following spine surgeries .
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However, studies have shown that COX-2 inhibitors do not inhibit spinal fusion or bone healing
and therefore is a safe analgesic to use following spine surgery. In fact, COX-2 inhibitors were
shown to provide better analgesia compared to tramadol without compromising bone healing .
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According to a meta-analysis done by Farii et al., the risk of nonunion was higher in patients
who received NSAIDs. However, when the studies were categorized into those who received
NSAIDs during the early postoperative period (less than 2 weeks) versus those who were
exposed to NSAIDs for a longer period of time (longer than 4 weeks), there was no significant
difference between those who received NSAIDs during the early postoperative period compared
to the control group while there was found to be a significant difference between those who
received NSAIDs for longer than 4 weeks compared to the control group. This study also showed
that the use of indomethacin did increase the risk of nonunion. Therefore, NSAIDs, other than
indomethacin, can be an excellent analgesic that can be safely used during the early
postoperative period .
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Ketorolac has been successful in controlling early surgical pain but in order to decrease
postoperative opioid consumption, patients required a dose higher than 60 mg. Although
effective, there are side effects of ketorolac that limits its universal use for regular use for
postoperative pain such as renal impairment. Ketorolac has also been associated with nonunion
and failed spinal fusion in patients with history of smoking as well 18, 19 .

Acetaminophen

Although the mechanism of action of acetaminophen is not entirely clear, its antipyretic and
analgesic property is well established. It has been historically categorized under NSAIDs
because of its ability to inhibit the cyclooxygenase pathways and provide analgesia. However
unlike NSAIDs, acetaminophen has weak anti-inflammatory activity which is the hallmark of
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inhibition, increase in pain threshold and its ability to modulate the endogenous cannabinoid
system, possibly by preventing COX-dependent endocannabinoid degradation . The
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recommended therapeutic dose for acetaminophen is 4 g to avoid hepatotoxicity and liver failure
as a result of glutathione depletion. Despite much debate regarding the superior efficacy of
intravenous over oral acetaminophen, it has been shown that there is no difference between oral
& intravenous administration when used as part of the 24-hour multimodal analgesic regimen
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after a total knee arthroplasty .

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