Preoperative Factors Associated with Remote Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort: Post Hoc Analysis of a Perioperative Gabapentin Trial

Jennifer M Hah,1 Heather Hilmoe,2 Peter Schmidt,2 Rebecca McCue,2 Jodie Trafton,3,4 Debra Clay,2 Yasamin Sharifzadeh,2 Gabriela Ruchelli,2 Tina Hernandez Boussard,5 Stuart Goodman,6 James Huddleston,7 William J Maloney,7 Frederick M Dirbas,8 Joseph Shrager,9 John G Costouros,7 Catherine Curtin,10 Sean C Mackey,1 Ian Carroll1 1Division of Pain Medicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, CA, USA; 2Stanford Systems Neuroscience and Pain Lab, Stanford University, Stanford, CA, USA; 3Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA; 4VA Program Evaluation and Resource Center, VHA Office of Mental Health Operations, Palo Alto, CA, USA; 5Department of Medicine, Department of Biomedical Data Science, Stanford University, Stanford, CA, USA; 6Department of Orthopaedic Surgery and (by Courtesy) Bioengineering, Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA; 7Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA; 8Department of General Surgery, Stanford University, Stanford, CA, USA; 9Division of Thoracic Surgery, Stanford University, Stanford, CA, USA; 10Division of Hand and Plastic Surgery, Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USACorrespondence: Jennifer M HahDivision of Pain Medicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, 1070 Arastradero Road, Suite 200, Palo Alto, CA 94304, USATel +1 650-736-9415Fax +1 650-725-9642Email jhah@stanford.eduBackground: Preoperative patient-specific risk factors may elucidate the mechanisms leading to the persistence of pain and opioid use after surgery. This study aimed to determine whether similar or discordant preoperative factors were associated with the duration of postoperative pain and opioid use.Methods: In this post hoc analysis of a randomized, double-blind, placebo-controlled trial of perioperative gabapentin vs active placebo, 410 patients aged 18– 75 years, undergoing diverse operations underwent preoperative assessments of pain, opioid use, substance use, and psychosocial variables. After surgery, a modified Brief Pain Inventory was administered over the phone daily up to 3 months, weekly up to 6 months, and monthly up to 2 years after surgery. Pain and opioid cessation were defined as the first of 5 consecutive days of 0 out of 10 pain or no opioid use, respectively.Results: Overall, 36.1%, 19.8%, and 9.5% of patients continued to report pain, and 9.5%, 2.4%, and 1.7% reported continued opioid use at 3, 6, and 12 months after surgery. Preoperative pain at the future surgical site (every 1-point increase in the Numeric Pain Rating Scale; HR 0.93; 95% CI 0.87– 1.00; P=0.034), trait anxiety (every 10-point increase in the Trait Anxiety Inventory; HR 0.79; 95% CI 0.68– 0.92; P=0.002), and a history of delayed recovery after injury (HR 0.62; 95% CI 0.40– 0.96; P=0.034) were associated with delayed pain cessation. Preoperative opioid use (HR 0.60; 95% CI 0.39– 0.92; P=0.020), elevated depressive symptoms (every 5-point increase in the Beck Depression Inventory-II score; HR 0.88; 95% CI 0.80– 0.98; P=0.017), and preoperative pain outside of the surgical site (HR 0.94; 95% CI 0.89– 1.00; P=0.046) were associated with delayed opioid cessation, while perioperative gabapentin promoted opioid cessation (HR 1.37; 95% CI 1.06– 1.77; P=0.016).Conclusion: Separate risk factors for prolonged post-surgical pain and opioid use indicate that preoperative risk stratification for each outcome may identify patients needing personalized care to augment universal protocols for perioperative pain management and conservative opioid prescribing to improve long-term outcomes.Keywords: persistent postsurgical pain, persistent postoperative opioid use, chronic opioid use after surgery, chronic pain after surgery