title: The effect of triple vs. double nonopioid therapy on postoperative pain and functional outcome after abdominal hysterectomy: a randomised double-blind control trial.
abstract: BACKGROUND
  Movement-evoked pain is more severe than pain at rest and is likely to interfere more with functional recovery after surgery.
  
  
  OBJECTIVE
  To compare triple vs. double nonopioid perioperative analgesic regimens in women undergoing abdominal hysterectomy.
  
  
  METHODS
  A randomised, parallel design, double-blind controlled trial.
  
  
  METHODS
  A single-centre trial. Study period from November 2009 to July 2013.
  
  
  METHODS
  Adults (>18 years) of American Society of Anesthesiologists' status 1 to 2 scheduled for abdominal hysterectomy.
  
  
  METHODS
  Patients were randomised to one of four study treatment groups: acetaminophen, meloxicam and gabapentin (AMG); acetaminophen and meloxicam; acetaminophen and gabapentin; and meloxicam and gabapentin. In addition to intravenous patient-controlled opioid analgesia, study treatments were administered for 48 h, starting 1 h preoperatively.
  
  
  METHODS
  The primary outcome was cough-evoked pain. Secondary outcomes included pain at rest, during sitting and peak expiration, opioid consumption, side effects, peak expiratory flow rate, timed up and go test (TUG), and modified Brief Pain Inventory (mBPI).
  
  
  RESULTS
  Interim analysis indicated a minimal chance of demonstrating superiority of the triple regimen group over all three double regimen groups if the trial were to be recruited to planned sample size. Thus, the trial was prematurely terminated for futility. All four analgesic regimens were well tolerated. Exploratory analyses revealed consistent significant negative correlations between pain and TUG and between pain and interference with activity, walking and sleep.
  
  
  CONCLUSIONS
  This trial failed to demonstrate substantial benefits with the addition of a third nonopioid analgesic to three different double-drug regimens. Further research is needed that will more definitively support expanding multimodal analgesic practices. Our results demonstrate consistent correlations between evoked pain and functional outcomes further emphasising the need for improved analgesic regimens that will accelerate postsurgical functional recovery.
  
  
  BACKGROUND
  International Standard Randomised Controlled Trial Number Register 12723675.
authors.affiliation: From the Department of Anesthesiology & Perioperative Medicine (IG, DD-S, SD, RR, EO), Department of Biomedical & Molecular Sciences (IG), Centre for Neuroscience Studies (IG), Department of Mathematics & Statistics (DT), and Department of Obstetrics & Gynaecology, Queen's University, Kingston, Ontario, Canada (MM).
authors.forename: Ian
authors.initials: I
authors.lastname: Gilron
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Deborah
authors.initials: D
authors.lastname: Dumerton-Shore
authors.forename: Scott
authors.initials: S
authors.lastname: Duggan
authors.forename: Rachel
authors.initials: R
authors.lastname: Rooney
authors.forename: Michael
authors.initials: M
authors.lastname: McGrath
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Orr
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use; D000328:Adult; D000588:Amines / Q000627:therapeutic use; D016058:Analgesia, Patient-Controlled / Q000009:adverse effects / Q000379:methods*; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D057239:Early Termination of Clinical Trials; D005260:Female; D000077206:Gabapentin; D006801:Humans; D007044:Hysterectomy / Q000009:adverse effects* / Q000379:methods; D000077239:Meloxicam; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects / Q000627:therapeutic use*; D009864:Ontario; D010147:Pain Measurement; D010149:Postoperative Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D020127:Recovery of Function; D013843:Thiazines / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
chemical_list: D000588:Amines; D000701:Analgesics, Opioid; D003509:Cyclohexanecarboxylic Acids; D013843:Thiazines; D013844:Thiazoles; D000082:Acetaminophen; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine; D000077239:Meloxicam