Paradoxical Hyperalgesia of Supra-orbital and Infra-orbital Nerve Blocks when Anesthetizing the Trigeminal Nerves in Trans-Sphenoidal Endonasal Pituitary Surgery: A Prospective, Randomized, Double-blinded Clinical Trial

Abstract Background: Pituitary neurosurgery executed via the transsphenoidal endonasal approach is commonly performed for pituitary adenomas. Reasons for prolonged hospital stay include postoperative migraine headache pain and protracted nausea with or without vomiting. Bilateral superficial trigeminal nerve blocks of the supra-orbital V1 and infra-orbital V2 (SION) nerves performed intra-operatively as a regional anesthetic adjunct to general anesthesia were hypothesized to reduce pain exposure and thus 6 hours post-operative morphine PCA (patient-controlled analgesia) use by patients. Methods: 49 patients, following induction of general anesthesia for their transsphenoidal surgery, were prospectively randomized in a double-blinded fashion to receive additional regional anesthesia as either a block (0.5% ropivacaine with epi 1:200,000) or placebo/sham (0.9% normal saline). The primary endpoint was the pain exposure and resulting systemic morphine PCA opioid consumption by the two groups in the first 6-hours post-operatively. The secondary endpoints included (1) incidence of post-operative nausea and vomiting and (2) time to eligibility for PACU discharge. Results: Of the 49 patients that were enrolled, 3 patients were excluded due to protocol violations. Ultimately, there was no statistically significant difference between morphine PCA use in the 6-hours post-operatively between the block and placebo/sham groups. There was, however, a slight visual tendency of the block group for higher pain scores, morphine use p=0.046, and delayed PACU discharge. False discovery rate corrected comparisons at each time point then revealed no statistically significant difference between the two groups. There were no differences between the two groups for secondary endpoints. Conclusion: 6-hour post-operative migraine headache pain after endoscopic trans-sphenoidal pituitary surgery likely has a more complicated mechanism involving more than the superficial trigemino-vascular system and perhaps is neuro-modulated by other brain nuclei. ClinicalTrials.gov NCT04670614, Date of Registration 17/12/2020