title: Postoperative pain after laparoscopic cholecystectomy is not reduced by intraoperative analgesia guided by analgesia nociception index (ANI®) monitoring: a randomized clinical trial.
abstract: BACKGROUND
  Laparoscopic cholecystectomy frequently results in significant immediate postoperative pain. A new pain monitor, analgesic nociception index (ANI®), based on heart rate variability, has recently been approved for intraoperative nociception monitoring. We designed a single-blind, parallel-group, randomized control trial to test the hypothesis that protocol-driven intraoperative analgesia guided by ANI during laparoscopic cholecystectomy would improve titration of intraoperative analgesics leading to decreased postoperative pain.
  
  
  METHODS
  One hundred and twenty consecutive adult participants presenting for elective laparoscopic cholecystectomy were recruited. Participants were randomly allocated by sealed envelope to receive intraoperative morphine either guided by ANI via a protocol (intervention group) or guided by the anaesthetist with ANI concealed (control group). All participants received paracetamol, parecoxib, fentanyl at induction, and local anaesthetic to port sites. The primary endpoint was the presence of moderate/severe pain (visual analogue scale ≥50 mm) at any of the four time points in the first postoperative hour. Secondary endpoints included postoperative rescue morphine.
  
  
  RESULTS
  Sixty participants were randomized to each group, and all but one drop-out from the intervention group were analysed. The usage of ANI guidance did not result in a decrease in the rate of moderate/severe pain (50.8% vs 45.0%: difference of -5.8%, 95% confidence interval, -23.7% to 12.1%, P=0.58), or the use of postoperative rescue analgesia.
  
  
  CONCLUSIONS
  This randomized control trial of intraoperative ANI-guided morphine administration in elective laparoscopic cholecystectomy failed to show any advantage over the current standard of care, and demonstrated a high level of postoperative pain, despite the use of multimodal analgesia.
  
  
  BACKGROUND
  ANZCTR Reference ACTRN12612000953831 (URL: http://www.anzctr.org.au/trial_view.aspx?ID=362949).
authors.affiliation: Peninsula Health, Hastings Road, Frankston, VIC 3199 Australia jszental@gmail.com.
authors.forename: J A
authors.initials: JA
authors.lastname: Szental
authors.affiliation: Peninsula Health, Hastings Road, Frankston, VIC 3199 Australia.
authors.forename: A
authors.initials: A
authors.lastname: Webb
authors.affiliation: Peninsula Health, Hastings Road, Frankston, VIC 3199 Australia.
authors.forename: C
authors.initials: C
authors.lastname: Weeraratne
authors.affiliation: Peninsula Health, Hastings Road, Frankston, VIC 3199 Australia.
authors.forename: A
authors.initials: A
authors.lastname: Campbell
authors.affiliation: Peninsula Health, Hastings Road, Frankston, VIC 3199 Australia.
authors.forename: H
authors.initials: H
authors.lastname: Sivakumar
authors.affiliation: Peninsula Health, Hastings Road, Frankston, VIC 3199 Australia.
authors.forename: S
authors.initials: S
authors.lastname: Leong
mesh_terms: D000328:Adult; D000368:Aged; D000698:Analgesia / Q000379:methods*; D017081:Cholecystectomy, Laparoscopic; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000295:instrumentation*; D010147:Pain Measurement / Q000295:instrumentation*; D010149:Postoperative Pain / Q000517:prevention & control*; D016037:Single-Blind Method
keywords: analgesics, opioid/therapeutic use; cholecystectomy, laparoscopic; heart rate; pain measurement/methods; pain, postoperative/drug therapy