In a randomized, double-blind, single-center, noninferiority trial, nonsteroidal anti-inflammatory drugs (NSAIDs) remarkably alleviated acute pain following transsphenoidal surgery, led to only a few noxious events, and reduced rescue opioid use in comparison with tramadol. Xiaopeng Guo et al. undertook this study for determining the noninferiority of NSAIDs to tramadol to control pain following transsphenoidal surgery for pituitary adenomas regarding analgesic efficacy, noxious events, and rescue opioid usage.

The study recruited 202 participants (age 18-70 years) with planned transsphenoidal surgery for pituitary adenomas and randomly segregated them (101 participants in each group) to receive either  NSAIDs (parecoxib injection and subsequent loxoprofen tablets) or tramadol (tramadol injection and subsequent tramadol tablets).

Pain score evaluated by a visual analog scale (VAS) for twenty-four hours following surgery was the major endpoint. Assessment of VAS scores for 48 and 72 hours were the secondary endpoints.

Vomiting,  skin rash,  nausea, gastrointestinal bleeding,  upset stomach, peptic ulcer, dizziness, and pethidine usage for controlling breakthrough pain were the other prespecified outcomes.

If the upper limit of 95% confidence interval of VAS score difference was < 1 point and the rate difference of noxious events and pethidine usage was < 5%, NSAIDs were considered to be non-inferior to tramadol. NSAIDs superiority was evaluated when noninferiority was verified. All the evaluations were carried out on an intention-to-treat basis.

The baseline characteristics between NSAIDs and tramadol groups were well-balanced. The mean VAS scores for twenty-four hours after surgery were lower in the NSAIDs group when compared to the tramadol group (-0.9 difference). For both secondary endpoints, noninferiority and superiority were also attained. In both groups, an improvement was noted in VAS scores over time.

Compared to the tramadol group, the NSAIDs group displayed a reduced occurrence of nausea, vomiting, and dizziness and a slightly elevated incidence of an upset stomach. Also, the percentage of opioid use was lower in the NSAIDs group vs. tramadol group, as shown in Table 1:

Thus, NSAIDs offer superior pain-mitigating effects compared to tramadol in people undergoing transsphenoidal surgery for pituitary adenomas.