Nonsteroidal antiinflammatory drugs versus tramadol in pain management following transsphenoidal surgery for pituitary adenomas: a randomized, double-blind, noninferiority trial

Xiaopeng Guo MD1,2,3,4, Zihao Wang MD1,2,3,4, Lu Gao MD1,2,3,4, Wenbin Ma MD1,2,3,4, Bing Xing MD1,2,3,4, and Wei Lian MD1,2,3,4
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  • 1 Department of Neurosurgery and
  • | 2 Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College;
  • | 3 China Pituitary Disease Registry Center; and
  • | 4 China Pituitary Adenoma Specialist Council, Beijing, China
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OBJECTIVE

Opioid-minimizing or nonopioid therapy using nonsteroidal antiinflammatory drugs (NSAIDs) or tramadol has been encouraged for pain management. This study aimed to examine the noninferiority of NSAIDs to tramadol for pain management following transsphenoidal surgery for pituitary adenomas in terms of analgesic efficacy, adverse events, and rescue opioid use.

METHODS

This was a randomized, single-center, double-blind noninferiority trial. Patients 18–70 years old with planned transsphenoidal surgery for pituitary adenomas were randomly assigned (in a 1-to-1 ratio) to receive NSAIDs (parecoxib injection and subsequent loxoprofen tablets) or tramadol (tramadol injection and subsequent tramadol tablets). The primary outcome was pain score assessed by a visual analog scale (VAS) for 24 hours following surgery; the secondary outcomes were VAS scores for 48 and 72 hours. Other prespecified outcomes included nausea, vomiting, dizziness, upset stomach, skin rash, peptic ulcer, gastrointestinal bleeding, and pethidine use to control breakthrough pain. Noninferiority of NSAIDs to tramadol was established if the upper limit of the 95% confidence interval (CI) of the VAS score difference was < 1 point and the rate difference of adverse events and pethidine use < 5%. The superiority of NSAIDs was assessed when noninferiority was verified. All analyses were performed on an intention-to-treat basis.

RESULTS

Two hundred two patients were enrolled between November 1, 2020, and May 31, 2021 (101 in the NSAIDs group, 101 in the tramadol group). Baseline characteristics between groups were well balanced. Mean VAS scores for 24 hours following transsphenoidal surgery were 2.6 ± 1.8 in the NSAIDs group and 3.5 ± 2.1 in the tramadol group (−0.9 difference, 95% CI −1.5 to −0.4; p value for noninferiority < 0.001, p value for superiority < 0.001). Noninferiority and superiority were also achieved for both secondary outcomes. VAS scores improved over time in both groups. Incidences of nausea (39.6% vs 61.4%, p = 0.002), vomiting (3.0% vs 42.6%, p < 0.001), and dizziness (12.9% vs 47.5%, p < 0.001) were significantly lower, while incidence of upset stomach (9.9% vs 2.0%, p = 0.017) was slightly higher in the NSAIDs group compared with the tramadol group. The percentage of opioid use was 4.0% in the NSAIDs group and 15.8% in the tramadol group (−11.8% difference, 95% CI −19.9% to −3.7%; p value for noninferiority < 0.001, p value for superiority = 0.005).

CONCLUSIONS

NSAIDs significantly reduced acute pain following transsphenoidal surgery, caused few adverse events, and limited opioid use compared with tramadol.

ABBREVIATIONS

CI = confidence interval; NSAID = nonsteroidal antiinflammatory drug; PUMCH = Peking Union Medical College Hospital; VAS = visual analog scale.

Illustration from Morshed et al. (pp 1–8). Copyright Ken Probst. Published with permission.

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  • 1

    Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2013-2017. Neuro Oncol. 2020;22(12)(suppl 2):iv1iv96.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Molitch ME. Diagnosis and treatment of pituitary adenomas: a review. JAMA. 2017;317(5):516524.

  • 3

    Buchfelder M, Schlaffer SM, Zhao Y. The optimal surgical techniques for pituitary tumors. Best Pract Res Clin Endocrinol Metab. 2019;33(2):101299.

  • 4

    Couldwell WT. Transsphenoidal and transcranial surgery for pituitary adenomas. J Neurooncol. 2004;69(1-3):237256.

  • 5

    Komotar RJ, Starke RM, Raper DM, Anand VK, Schwartz TH. Endoscopic endonasal compared with microscopic transsphenoidal and open transcranial resection of giant pituitary adenomas. Pituitary. 2012;15(2):150159.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Park IJ, Kim G, Ko G, Lee YJ, Hwang SH. Does preoperative administration of gabapentin/pregabalin improve postoperative nasal surgery pain?. Laryngoscope. 2016;126(10):22322241.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Yayik AM, Yildirim H, Ahiskalioglu A, Sakat MS, Ergüney ÖD, Ahiskalioglu EO, et al. Effects of bupivacaine versus bupivacaine plus dexamethasone-soaked nasal packing after endoscopic nasal surgery. J Craniofac Surg. 2019;30(4):11741177.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Shepherd DM, Jahnke H, White WL, Little AS. Randomized, double-blinded, placebo-controlled trial comparing two multimodal opioid-minimizing pain management regimens following transsphenoidal surgery. J Neurosurg. 2018;128(2):444451.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Breivik H, Stubhaug A. Management of acute postoperative pain: still a long way to go!. Pain. 2008;137(2):233234.

  • 10

    Joshi GP, Ogunnaike BO. Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain. Anesthesiol Clin North America.2005;23(1):2136.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Flexman AM, Ng JL, Gelb AW. Acute and chronic pain following craniotomy. Curr Opin Anaesthesiol. 2010;23(5):551557.

  • 12

    Haldar R, Kaushal A, Gupta D, Srivastava S, Singh PK. Pain following craniotomy: reassessment of the available options. BioMed Res Int. 2015;2015:509164.

  • 13

    Rahimi SY, Alleyne CH, Vernier E, Witcher MR, Vender JR. Postoperative pain management with tramadol after craniotomy: evaluation and cost analysis. J Neurosurg. 2010;112(2):268272.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Tsaousi GG, Logan SW, Bilotta F. Postoperative pain control following craniotomy: a systematic review of recent clinical literature. Pain Pract. 2017;17(7):968981.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Jeffrey HM, Charlton P, Mellor DJ, Moss E, Vucevic M. Analgesia after intracranial surgery: a double-blind, prospective comparison of codeine and tramadol. Br J Anaesth. 1999;83(2):245249.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Stoneham MD, Cooper R, Quiney NF, Walters FJ. Pain following craniotomy: a preliminary study comparing PCA morphine with intramuscular codeine phosphate. Anaesthesia. 1996;51(12):11761178.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Glare P, Aubrey KR, Myles PS. Transition from acute to chronic pain after surgery. Lancet. 2019;393(10180):15371546.

  • 18

    Reid C, Davies A. The World Health Organization three-step analgesic ladder comes of age. Palliat Med. 2004;18(3):175176.

  • 19

    Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c869.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Sarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol Int. 2019;13(4):353390.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Stevens PE, Levin A. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013;158(11):825830.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Chawla LS, Bellomo R, Bihorac A, Goldstein SL, Siew ED, Bagshaw SM, et al. Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup. Nat Rev Nephrol. 2017;13(4):241257.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Williams DL, Pemberton E, Leslie K. Effect of intravenous parecoxib on post-craniotomy pain. Br J Anaesth. 2011;107(3):398403.

  • 24

    Na HS, An SB, Park HP, Lim YJ, Hwang JW, Jeon YT, Min SW. Intravenous patient-controlled analgesia to manage the postoperative pain in patients undergoing craniotomy. Korean J Anesthesiol. 2011;60(1):3035.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Molnár C, Simon É, Kazup Á, Gál J, Molnár L, Novák L, et al. A single preoperative dose of diclofenac reduces the intensity of acute postcraniotomy headache and decreases analgesic requirements over five postoperative days in adults: a single center, randomized, blinded trial. J Neurol Sci. 2015;353(1-2):7073.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Hassani E, Mahoori A, Sane S, Tolumehr A. Comparison the effects of paracetamol with sufentanil infusion on postoperative pain control after craniotomy in patients with brain tumor. Adv Biomed Res. 2015;4:64.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Morad A, Winters B, Stevens R, White E, Weingart J, Yaster M, Gottschalk A. The efficacy of intravenous patient-controlled analgesia after intracranial surgery of the posterior fossa: a prospective, randomized controlled trial. Anesth Analg. 2012;114(2):416423.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Peng K, Jin XH, Liu SL, Ji FH. Effect of intraoperative dexmedetomidine on post-craniotomy pain. Clin Ther. 2015;37(5):11141121.e1.

  • 29

    Yadav G, Choupoo S, Das SK, Das SK, Behera SS, Khuba S, et al. Evaluating the role of flupirtine for postcraniotomy pain and compare it with diclofenac sodium: a prospective, randomized, double blind, placebo-controlled study. J Neurosurg Anesthesiol. 2014;26(1):3236.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    An LX, Chen X, Ren XJ, Wu HF. Electro-acupuncture decreases postoperative pain and improves recovery in patients undergoing a supratentorial craniotomy. Am J Chin Med. 2014;42(5):10991109.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Jirarattanaphochai K, Jung S. Nonsteroidal antiinflammatory drugs for postoperative pain management after lumbar spine surgery: a meta-analysis of randomized controlled trials. J Neurosurg Spine. 2008;9(1):2231.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Titsworth WL, Abram J, Guin P, Herman MA, West J, Davis NW, et al. A prospective time-series quality improvement trial of a standardized analgesia protocol to reduce postoperative pain among neurosurgery patients. J Neurosurg. 2016;125(6):15231532.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Jirarattanaphochai K, Thienthong S, Sriraj W, Jung S, Pulnitiporn A, Lertsinudom S, Foocharoen T. Effect of parecoxib on postoperative pain after lumbar spine surgery: a bicenter, randomized, double-blinded, placebo-controlled trial. Spine (Phila Pa 1976).2008;33(2):132139.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34

    De Benedittis G, Lorenzetti A, Migliore M, Spagnoli D, Tiberio F, Villani RM. Postoperative pain in neurosurgery: a pilot study in brain surgery. Neurosurgery. 1996;38(3):466470.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Pledger CL, Elzoghby MA, Oldfield EH, Payne SC, Jane JA Jr. Prospective comparison of sinonasal outcomes after microscopic sublabial or endoscopic endonasal transsphenoidal surgery for nonfunctioning pituitary adenomas. J Neurosurg. 2016;125(2):323333.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36

    Rigante M, Massimi L, Parrilla C, Galli J, Caldarelli M, Di Rocco C, Paludetti G. Endoscopic transsphenoidal approach versus microscopic approach in children. Int J Pediatr Otorhinolaryngol. 2011;75(9):11321136.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Higgins TS, Courtemanche C, Karakla D, Strasnick B, Singh RV, Koen JL, Han JK. Analysis of transnasal endoscopic versus transseptal microscopic approach for excision of pituitary tumors. Am J Rhinol. 2008;22(6):649652.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Trotti A, Colevas AD, Setser A, Basch E. Patient-reported outcomes and the evolution of adverse event reporting in oncology. J Clin Oncol. 2007;25(32):51215127.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

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